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					Table of Contents
Conference Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
Conference Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .3
Conference Co-Chairs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4
Conference Organizing Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .4
Scientific Program Committee . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
Executive Staff . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .5
Invited Presenters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .6
General Information . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
     American with Disabilities Act . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
     Conference Information Desk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
     Conference Location . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
     Continuing Medical Education (CME) Accreditation . . . . . . . . . . . . . . . . . . . . . . . . . . . . .9
     Exhibit Hall . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
     Messages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
     No Smoking Policy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
     Poster Sessions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
     Press Room . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
     Program and Abstracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
     Registration Fees and Hours . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
     Speaker Ready Room and Audiovisual Equipment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
     Verification of Attendance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
Affiliated Events and Other Meetings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .11
Hotel Floorplan . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .12
Program At-A-Glance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13
Final Program . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14
Meet the Experts Presenters . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .39
Abstracts
     Abstracts of Invited Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .45
     Abstracts of Oral Submitted Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .57
     Abstracts of Submitted Poster Presentations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .67
Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .94
Disclosure Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .99
                                                                                                                                      1
      Eighth Annual Conference
Conference Overview
The remarkable pace of biotechnology discovery is continuing unabated. New cytokines are identified, immune regulatory
pathways unraveled, promising adjuvants reported, and investigational products revealed to have high degrees of protection
for humans against viral diseases not yet vaccine preventable, such as human papilloma virus and herpes simplex. The tools
of vaccination are being applied therapeutically for various cancers and chronic conditions.

The Annual Conference on Vaccine Research provides high-quality, current reports of scientific progress featured in both
invited presentations and submitted abstracts. The disparate fields covered in both human and veterinary vaccinology
encourage valuable cross-fertilization of ideas and approaches among researchers otherwise focused on specific diseases or
methods.

The Conference has become the largest scientific meeting devoted exclusively to research on vaccines and associated
technologies for disease prevention and treatment through immunization. The Eighth Annual Conference promises to
maintain this tradition as the premier venue for cutting edge topics and issues. International experts will lead seminars and
panel discussions on topical areas of basic immunology, product development, clinical testing, regulation, and other aspects
of vaccine research. Opportunities for networking and scientific collaboration critical to advancing vaccine science and
development will be available through audience discussions, meet the experts breakfast sessions, poster presentations,
sponsored exhibits, evening ceremonies, and receptions



Conference Objectives
Overall Conference Objectives                                               s   Understand the role of functional antibodies in protection of humans against
                                                                                disease caused by encapsulated bacteria and how conjugate vaccines, in
At the conclusion of this conference, participants should be able to
                                                                                contrast to polysaccharide vaccines elicit antibody responses in young infants
meet the following objectives:                                              s   Know the role of T cells in providing immunological help to B cells stimulated
s Discuss recent scientific advances that are contributing to progress in
                                                                                by conjugate vaccines
    the development of vaccines                                             s   Discuss target antigens of Bacillus anthracis that can serve as the basis for
s Identify research opportunities and scientific challenges associated
                                                                                new and improved anthrax vaccines and the general advantages of
    with vaccine development, production, and distribution                      conjugate vaccines as a vaccinology strategy
                                                                            s   Understand the efficacy of conjugate pneumococcal vaccines in rural Africa
Session Specific Objectives                                                     and consider the implications for vaccination policies
Keynote Address
s Identify needs and challenges associated with vaccine use, and to         Update on Vaccines Against Enteric and Oral Infections
  demonstrate the reasons that research and development of new              s Provide an update on the current status of knowledge of rotavirus vaccine
  vaccines must be intensified                                                development and clinical trials, and know the challenges which remain for
                                                                              the future introduction of rotavirus vaccines
                                                                            s Understand the impact of norovirus infection on different populations,
Mary Lou Clements-Mann Memorial Lecture in Vaccine Sciences
s Define the burden of bacterial pneumonia using conjugate vaccines           barriers to the development of vaccines to prevent norovirus infection, and
  as probes                                                                   identify potential norovirus vaccine candidates
                                                                            s Know the rationale for developing a vaccine to prevent clostridium difficile

Conjugate Vaccine Issues                                                      associated diarrhea; the approach to vaccine development; and the results
s Understand the methods used for measuring vaccine efficacy under            of early clinical trials
                                                                            s Understand the basic microbial pathogenesis of dental caries, the basic
  condition of routine use in the UK; how the efficacy estimates have
  been used to help our understanding of the correlates of protection;        approaches to prevent dental caries, and the statues of preclinical and
  and how transmission models of diseases such as meningococcal               clinical studies aimed at developing immunologic means of preventing
  serogroup C can assist in understanding the impact of a vaccination         dental caries, especially regarding the development of mucosal anti-caries
  programme at the population level                                           vaccines


2
on Vaccine Research
Influenza and Vaccines for Emergency Pandemics                           s   Determine mechanisms which are responsible for the weaker and
s Understand how vaccine use in poultry will aid in control of the           shorter duration of B cell responses in early life
   H5N1 avian influenza outbreak in Asia and reduce risk for human       s   Learn the current state of knowledge about the molecular basis for the
   infections                                                                poor quality of antiviral antibodies made in response to viral infection
s Review the epidemiology of West Nile virus in North America
s Understand the regulatory considerations for the emergency use of      Multi-Agent and Chimeric Vaccines
   veterinary vaccines (biologics) in the United States                  s Provide an update on the progress towards an HIV/AIDS vaccine
                                                                         s Utlilize new understandings of immunology to develop vaccines based

Concrete Proposals for Ensuring a Secure Supply                            on novel technology
of Vaccines in the U.S.                                                  s Demonstrate that directed molecular evolution creates better vaccines by
s Describe the issues and possible solutions needed to limit shortages     recombining genes and selecting chimeric molecules for improved
   and strengthen vaccine supply in the United States; report on           vaccine efficacy
   progress made in the last three years; and to address current         s Explain the principles underlying use of yellow fever 17D as a live vector

   challenges                                                              for foreign genes, and discuss the status of development and clinical
s List six consensus policy recommendations to strengthen adult            testing of new vaccines against dengue, West Nile and Japanese
   immunization in the U.S. and how, after years of discussion             encephalitis.
   without agreement, a consensus policy agenda was achieved

Vaccinology of Neglected Diseases: Malaria
s Understand the rationale, background and recent progress with
  the RTS,S malaria vaccine and to provide an overview of the next
  steps in its clinical development
s Acknowledge that vaccines bearing single pre-erythrocytic
  antigens are capable of impacting parasitologic as well as clinical
  outcomes under conditions of natural malaria exposure.
s Describe the safety and immunologic profiles of recent adjuvants       Acknowledgments                                (as of April 20, 2005)
  that have been clinically evaluated in the context of malaria          This conference is supported, in part, through unrestricted educational
  vaccines
                                                                         grants from:
Therapeutic Vaccines
s Explain the status of the development of preventive and
                                                                         s   Acambis
  therapeutic vaccines for HPV induced cervical cancer and the           s   Aeras Global TB Vaccine Foundation
  basic immunology that is needed to guide these vaccine                 s   Antigenics, Inc.
  developments                                                           s   Baxter Healthcare
s Identify a therapeutic vaccine approach for treatment of               s   Becton Dickinson
  Alzheimer's disease                                                    s   Bill & Melinda Gates Foundation
s Summarize the current status of and challenges to the                  s   Chiron Vaccines
  development of vaccines for Type 1 diabetes                            s   Coley Pharmaceutical Group
s Describe the huge disease burden associated with HCV infection         s   Dynport Vaccine Company
  in the US and globally; and vaccine formulations designed to           s   EpiVax, Inc.
  boost cross-neutralizing antibody titers and broadly reactive          s   GlaxoSmithKline
  cellular immune responses
s Discuss the design of clinical trials underway and planned for
                                                                         s   Globe Immune, Inc.
  novel immunotherapy strategies
                                                                         s   Iomai Corporation
                                                                         s   MedImmune, Inc.
Vaccinology Impact of Recent Advances in Immunology                      s   Merck & Co., Inc.
s Understand the process of innate imprinting and its potential          s   Protein Sciences Corporation
  application to the treatment of inflammatory disease                   s   sanofi pasteur
s Identify the main limitations which limit neonatal and infant IgG      s   U.S. Food and Drug Administration
  responses to immunization and gain understanding in the                s   VaxGen, Inc
  experimental approaches that may be used to study the                  s   Vical, Inc.
  determinants of such limitations                                       s   Wyeth Pharmaceuticals


                                                                                                                                                    3
     Eighth Annual Conference
                                                  Conference Co-Chairs
                                                    Peter L. Nara, D.V.M., Ph.D.
                                                  Biological Mimetics, Inc., Frederick, Maryland

                                                    N. Regina Rabinovich, M.D.
                                             Bill and Melinda Gates Foundation, Seattle, Washington

                                                        Susan J. Rehm, M.D.
                                        National Foundation for Infectious Diseases, Bethesda, Maryland

                                                        Bruce G. Weniger, M.D.
                                           Centers for Disease Control and Prevention, Atlanta, Georgia




Conference Organizing Committee
John D. Clemens, M.D.                                                          Peter L. Nara, D.V.M., Ph.D.
International Vaccine Institute                                                Conference Co-Chair
Seoul, Korea
                                                                               Gregory A. Poland, M.D.
Cyril Gerard Gay, D.V.M., Ph.D.                                                International Society for Vaccines
U.S. Department of Agriculture                                                 Rochester, Minnesota
Beltsville, Maryland
                                                                               N. Regina Rabinovich, M.D.
Myron M. Levine, M.D., D.T.P.H.                                                Conference Co-Chair
Center for Vaccine Development
Baltimore, Maryland                                                            Susan J. Rehm, M.D.
                                                                               Conference Co-Chair
Dean D. Mason
Albert B. Sabin Vaccine Institute                                              Darshna Tanna
Washington, DC                                                                 Fondation Mérieux
                                                                               Lyon Cedex, France
Pamela M. McInnes, D.D.S., M.Sc.
National Institute of Allergy and Infectious Diseases                          Bernard A.M. Van der Zeijst, Ph.D.
Bethesda, Maryland                                                             Netherlands Vaccine Institute
                                                                               Bilthoven, Netherlands
Karen Midthun, M.D.
Center for Biologics Evaluation and Resesarch                                  Bruce G. Weniger, M.D.
Bethesda, Maryland                                                             Conference Co-Chair




4
on Vaccine Research
Scientific Program Committee
Lorne A. Babiuk, Ph.D.                         Susan J. Rehm, M.D.
Vaccine and Infectious Disease Organization    Conference Co-Chair
Saskatoon, Canada
                                               Harriet L. Robinson, Ph.D.
Carol J. Baker, M.D.                           Emory University School of Medicine
Baylor College of Medicine                     Atlanta, Georgia
Houston, Texas
                                               Connie Schmaljohn, Ph.D.
Richard J. Duma, M.D., Ph.D.                   U.S. Army Medical Research
Halifax Medical Center                         Institute of Infectious Diseases
Daytona Beach, Florida                         Frederick, Maryland

Hana Golding, Ph.D.                            Alan R. Shaw, Ph.D.
Center for Biologics Evaluation and Research   Merck & Company, Inc.
Bethesda, Maryland                             West Point, Pennsylvania

Diane E. Griffin, M.D., Ph.D.                  George R. Siber, M.D.
Johns Hopkins University                       Wyeth-Lederle Vaccines
Bloomberg School of Public Health              Pearl River, New York
Baltimore, Maryland
                                               Bruce G. Weniger, M.D.
Paul-Henri Lambert, M.D.                       Conference Co-Chair
Centre Medical Universitaire de Genéve
Geneva, Switzerland

Myron M. Levine, M.D., D.T.P.H.                NFID Executive Staff
Member, Conference Organizing Committee
                                               Sharon Cooper-Kerr
Pamela M. McInnes, D.D.S.                      Director, Events Planning
Member, Conference Organizing Committee        National Foundation for Infectious Diseases
                                               Bethesda, Maryland
Peter L. Nara, D.V.M., Ph.D.
Conference Co-Chair
                                               Sheena L. Majette
Stanley A. Plotkin, M.D.                       Director, Continuing Medical Education
University of Pennsylvania                     National Foundation for Infectious Diseases
Doylestown, Pennsylvania                       Bethesda, Maryland

N. Regina Rabinovich, M.D.                     Len Novick
Conference Co-Chair                            Executive Director
                                               National Foundation for Infectious Diseases
Rino Rappuoli, Ph.D.                           Bethesda, Maryland
IRIS, Chiron, SpA
Sienna, Italy


                                                                                             5
     Eighth Annual Conference
Invited Presenters*
Robert L. Atmar, M.D.                                             David Goldblatt M.D., Ph.D.
Associate Professor                                               Professor of Vaccinology and Immunology
Departments of Medicine and Molecular Virology and Microbiology   Institute of Child Health
Baylor College of Medicine                                        University College London
Houston, TX                                                       London, United Kingdom

W. Ripley Ballou, M.D.                                            Lt. Col. Donald Gray Heppner, M.D.
Vice President                                                    Director, Malaria Vaccine Program
Clinical Research and Development, Emerging Diseases              Department of Immunology
GlaxoSmithKline Biologicals                                       Walter Reed Army Institute of Research
Rixensart, Belgium                                                Silver Spring, MD

Alan D.T. Barrett, Ph.D.                                          David L. Heymann, M.D.
Professor and Vice Chairman for Research                          Executive Director
Department of Pathology                                           Communicable Diseases
Associate Director, Sealy                                         World Health Organization
Center for Vaccine Development                                    Geneva, Switzerland
University of Texas Medical Branch
Galveston TX                                                      Richard E. Hill, Jr., D.V.M.
                                                                  Director
James E. Crowe, Jr. M.D.                                          Center for Veterinary Biologics
Professor of Pediatrics                                           USDA, Animal and Plant Health Inspection Service
Vanderbilt University School of Medicine                          Ames, IA
Nashville, TN
                                                                  Michael Houghton, Ph.D.
Felicity Cutts, Ph.D.                                             Vice President and Fellow
Professor                                                         Hepatitis C Research
Initiative for Vaccine Research                                   Chiron Corporation
World Health Organization                                         Emeryville, CA
Prevessin-Moens, Switzerland
                                                                  Tracy Hussell, Ph.D.
Giuseppe Del Giudice, M.D.                                        Reader, Kennedy Institute
Vice President, Serology and Animal Model                         Technology and Medicine
Chiron Vaccines                                                   Imperial College of Science
Siena, Italy                                                      London, England

Filip Dubovsky M.D., M.P.H.                                       Richard A. Insel, M.D.
Scientific Director                                               Executive Vice President of Research
Malaria Vaccine Initiative, PATH                                  Juvenile Diabetes Research Foundation International
Bethesda, MD                                                      New York, NY




6
on Vaccine Research
Invited Presenters*
David R. Johnson, M.D., M.P.H.                       Christopher P. Locher Ph.D.
Director, Scientific & Medical Affairs               Project Leader
sanofi pasteur                                       Department of Infectious Diseases
Swiftwater, PA                                       Maxygen, Inc.
                                                     Redwood City, CA
Stefan H.I. Kappe, Ph.D.
Independent Investigator                             Suzanne M. Michalek, Ph.D.
Affiliate Professor of Pathobiology                  Professor
University of Washington                             Department of Microbiology
Seattle Biomedical Research Institute                University of Alabama at Birmingham
Seattle, WA                                          Birmingham, AL

W. Martin Kast, Ph.D.                                Elizabeth Miller, M.D.
Walter A. Richter Cancer Research Chair              Head, Immunization Deparatment
Professor of Molecular Microbiology and Immunology   Health Protection Agtency
Norris Comprehensive Cancer Center                   Communicable Disease Surveillance Center
University of Southern California                    London, United Kingdom
Los Angeles, CA
                                                     Thomas P. Monath, MD
Jerome O. Klein, M.D.                                Chief Scientific Officer
Professor and Vice Chairman for Academic Affairs     Acambis, Inc.
Department of Pediatrics                             Cambridge, MA
Boston Medical Center
Boston, MA                                           Albert D.M.E. Osterhaus, D.V.M., Ph.D.
                                                     Head, Department of Virology
Keith P. Klugman, MD, PhD                            Erasmus University Rotterdam
Professor, Infectious Diseases                       Rotterdam, Netherlands
Department of International Health
Emory University                                     John Robbins, M.D.
Atlanta, GA                                          Chief
                                                     Laboratory Development and Molecular Immunology
Karen L. Kotloff, MD                                 NICHD/National Institutes of Health
Professor of Pediatrics and Medicine                 Bethesda, MD
Center for Vaccine Development
University of Maryland School of Medicine            Harriet L. Robinson, PhD
Baltimore, MD                                        Asa Griggs Candler Professor
                                                     Chief, Division of Microbiology and Immunology
Antonio Lanzavecchia, M.D.                           Yerkes Regional Primate Research Center
Director                                             Emory University
Institute for Research in Biomedicine                Atlanta, GA
Bellinzona, Switzerland




                                                                                                       7
     Eighth Annual Conference
Invited Presenters*
Dale Schenk, Ph.D.
Senior Vice President
Chief Scientific Officer
Elan Pharmaceuticals
South San Francisco, CA

John W. Shiver, Ph.D.
Vice President
Vaccine and Biologics Research
Merck and Company, Inc.
West Point, PA

Claire-Anne Siegrist, M.D.
Professor of Vaccinology
Director of the Pediatric Department, Director of the WHO
Collaborating Center for Neonatal Vaccinology
University of Geneva, CMU
Geneva, Switzerland

Duncan Steele, M.D.
Scientist and Responsible Officer
Department of Immunization, Vaccines and Biologicals
World Health Organization
Geneva, Switzerland

David E. Swayne, D.V.M., Ph.D.
Laboratory Director
Southeast Poultry Research Laboratory
USDA, Agricultural Research Service
Athens, GA




*Speakers and presentations subject to change




8
on Vaccine Research
General Information
AMERICANS WITH DISABILITIES ACT
The Baltimore Marriott Inner Harbor Hotel is fully accessible to the public in accordance with the Americans
with Disabilities Act guidelines. If you have any special meeting needs or requirements, please contact either
Sharon Cooper-Kerr or a member of the hotel staff.


CONFERENCE INFORMATION DESK
The Conference Information Desk is located in the foyer area outside the Grand Ballroom. Conference staff
will be available at the desk throughout the conference.


CONFERENCE LANGUAGE
The official language for the conference is English.


CONFERENCE LOCATION
All sessions of the conference will be held at:

                                     Baltimore Marriott Inner Harbor Hotel
                                     110 South Eutaw Street
                                     Baltimore, Maryland 21201
                                     (410) 962-0202


GENERAL CME INFORMATION
The National Foundation for Infectious Diseases (NFID) is accredited by the Accreditation Council for
Continuing Medical Education (ACCME) to provide Continuing Medical Education (CME) for physicians.
NFID takes responsibility for the content, quality, and scientific integrity of this CME activity.

NFID designates this CME activity for a maximum of 21 Category 1 credits toward the AMA Physician’s
Recognition Award. Each physician should claim only those hours of credit that he/she actually spent in the
educational activity.

Designated CME Activities
Sessions designated with a CME        symbol have been approved for CME Credit. No other sessions are
eligible for CME credit hours.

CME Certificates
In order to ensure that you receive the CME credit hours to which you are entitled, please note the following:
1. Complete the CME application for credits located at the Conference Information Desk.
2. Return your completed application and conference evaluation to conference staff at the Conference
   Information Desk.



                                                                                                                 9
      Eighth Annual Conference
CME Disclosures
In order for program sessions to be accredited, program presenters must disclose to the conference participants
any real or apparent conflict(s) of interest related to the content of their presentations. A summary of these
conflicts of interest is printed separately in this book under the heading Continuing Medical Education
Disclosures (see Table of Contents).



EXHIBIT HALL
Visit the Exhibit Hall to meet with representatives from companies displaying the latest technologies in vaccine-
related products and services. The exhibit hall hours are Tuesday, May 10, 10:30 a.m. – 3:30 p.m.; and
Wednesday, May 11, 10:00 a.m. – 3:30 p.m. A prize drawing will be held on Wednesday, May 11, at 1:15 p.m.
Be sure to get your exhibitor passport stamped by each of the exhibitors to qualify for the drawing and return to
the conference registration desk by 1:00 p.m., Wednesday, May 11.



MESSAGES
All sleeping rooms in the Baltimore Marriott Inner Harbor Hotel are equipped with a voice mail system. This
system is accessible via the hotel operator using the house phone. In case of emergencies requiring immediate
attention, your party should call the general hotel number listed below and instruct the switchboard to deliver a
message to Sharon Cooper-Kerr or Sheena Majette at the Vaccine Research Conference Information Desk
outside of the Grand Ballroom. The general hotel number is 1-410-962-0202.



NO SMOKING POLICY
The Baltimore Marriott Inner Harbor Hotel is a non-smoking facility except for specially designated guest
rooms and smoking areas of the hotel bars and restaurants. No smoking is allowed in any of the session rooms,
coffee break area or in the foyer adjoining the session rooms.



POSTER SESSIONS
Posters will be on display on Monday, May 9 from 10:30 a.m. – 11:30 a.m. Presenters will be at their boards
during this time to answer questions and discuss their research. There will also be a poster reception at
5:30 p.m. on Monday which will conclude the poster program. Posters and the Reception will be located in
the Stadium Ballroom located on the second floor of the hotel.



PRESS ROOM
NFID will have a Press Room located in the Westminster Room. Members of the press should sign in at the
Conference Information Desk during registration hours.



PROGRAM AND ABSTRACTS
Each registered participant will receive one complimentary copy of the Final Program and Abstract Book as part
of his/her registration fee. Additional copies, if available, can be purchased for $25. Orders for additional
copies can be taken at the Conference Information Desk starting Tuesday, May 10, and after the conference by
e-mail to vaccine@nfid.org, phone at (301) 656-0003 x19, or by fax at (301) 907-0878.
10
on Vaccine Research
REGISTRATION FEES AND HOURS
The onsite registration fee: US $450.00 (Non Member) and $405.00 (NFID Supporting Member)

Space is limited to the first 525 registrants. The registration fee includes a program/abstract book, continental
breakfast on each day of the conference, all scheduled coffee breaks, lunch presentation on Monday, and the
receptions on Monday and Tuesday. Accommodations and additional meals (i.e. lunch) are not included.
Individuals interested in registering onsite may do so at the Conference Information Desk between the
following times:
        Sunday, May 8 . . . . . . . . . . . . . . . . . . . . .7:00 p.m. - 9:00 p.m.
        Monday, May 9 . . . . . . . . . . . . . . . . . . . .7:00 a.m. - 5:00 p.m.
        Tuesday, May 10 . . . . . . . . . . . . . . . . . . . .7:00 a.m. - 5:00 p.m.
        Wednesday, May 11 . . . . . . . . . . . . . . . . .7:30 a.m. - noon


Speaker Ready Room and Audiovisual Equipment
A room has been set aside for speakers to preview their slides. All speakers should check in at the Conference
Information Desk to be directed to the speaker ready room. The room will be open during the registration
hours and will be equipped with a laptop for preview of your PowerPoint presentation.
Standard session room setup includes a PC, 250 zip drive, LCD projector, laser pointer, podium microphone,
and aisle microphone.


Verification of Attendance
International attendees may obtain a letter of attendance verification from the staff at the Conference
Information Desk during registration hours.



Affiliated Events and Other Meetings
MONDAY, MAY 9, 2005
Conference on Vaccine Research Organizing and Scientific Program Committees Meeting
(Closed meeting)
6:00 p.m. – 9:00 p.m.
Patapsco/Severn Rooms



TUESDAY, MAY 10, 2005
Albert B. Sabin Vaccine Institute Award Ceremony and Reception
6:00 p.m. – 7:00 p.m., Grand Ballroom Foyer (Reception)
7:00 p.m. - 8:00 p.m., Grand Ballroom (Ceremony)




                                                                                                                 11
     Eighth Annual Conference
            Hotel Floor Plan




12
on Vaccine Research
                                       PROGRAM-AT-A-GLANCE

        SUNDAY, MAY 8         MONDAY, MAY 9                   TUESDAY, MAY 10                WEDNESDAY, MAY 11

7:00                    Registration                  Registration                      Meet the Experts
                                                      Meet the Experts                  Breakfast Session
                                                      Breakfast Session
7:30                    Poster Set-up                 Continental Breakfast             Registration
                                                                                        Continental Breakfast/Exhibits
8:00                    Continental Breakfast         Symposium 3:                      Symposium 6:
                                                      Influenza and Vaccines            Therapeutic Vaccines
                                                      for Emergency Pandemics

8:30                    Welcome and Introductions
8:35                    Keynote Address
9:20                    Mary Lou Clements-Mann
                        Memorial Lecture
10:00                   Coffee Break                                                    Coffee Break/Exhibits
10:30                   Poster Session                Coffee Break/Exhibits             Submitted Presentations 3&4
11:00                                                 Submitted Presentations 1&2
11:45                   Charles Mérieux
                        Award Luncheon
12:00                                                                                   Lunch (on your own)
12:30                                                 Lunch (on your own)
1:00                    Symposium 1:                                                    Symposium 7:
                        Conjugate Vaccine Issues                                        Vaccinology Impact of Recent
                                                                                        Advances in Immunology
1:30                                                  Symposium 4:
                                                      Concrete Proposals for Ensuring
                                                      a Secure Supply of Vaccines
                                                      in the U.S.

3:00                    Coffee Break                  Coffee Break/Exhibits             Coffee Break/Exhibits
3:30                    Symposium 2:                  Symposium 5:                      Symposium 8:
                        Update on Vaccines Against    Vaccinology of Neglected          Multi-Agent and Chimeric Vaccines
                        Enteric and Oral Infections   Diseases: Malaria
5:30                    Adjournment                   Adjournment                       Adjournment/Participant Evaluation
                        Poster Reception
6:00                                                  Albert B. Sabin Vaccine
                                                      Institute Reception
7:00    Registration                                  Presentation of the
                                                      Albert B. Sabin Gold Medal



                                                                                                                             13
     Eighth Annual Conference
                                                    FINAL PROGRAM

 SUNDAY, MAY 8, 2005
     7:00 p.m. – 9:00 p.m. Early Registration
                                                                                                     Grand Ballroom Foyer


 MONDAY, MAY 9, 2005
     7:00 a.m. – 5:00 p.m. Registration                                                              Grand Ballroom Foyer

     7:30 a.m.              Poster Set-Up                                                                  Stadium Ballroom

     8:00 a.m.              Continental Breakfast                                                   Grand Ballroom Foyer

     8:30 a.m.              Welcome and Introductions                                                       Grand Ballroom
                            Susan J. Rehm, M.D.
                            National Foundation for Infectious Diseases
                            Bethesda, MD

 Keynote Address               CME                                                                          Grand Ballroom
                            Moderator:          Bruce G. Weniger, M.D.
                                                Centers for Disease Control and Prevention

     8:35 a.m.       1.     Dilemmas in Public Health: From Smallpox to Polio, SARS, and Avian Influenza
                            David L. Heymann, M.D.
                            World Health Organization
                            Geneva, Switzerland

     9:10 a.m.              Questions and Answers

 Mary Lou Clements-Mann Memorial Lecture in Vaccine Sciences CME                                            Grand Ballroom
                            Moderator:          George R. Siber, M.D.
                                                Wyeth-Lederle Vaccines

     9:20 a.m.       2.     Use of Conjugate Vaccines as a Probe to Define the Role of the
                            Pneumococcus in the Etiology of Pneumonia
                            Keith P. Klugman, M.D., Ph.D.
                            Emory University, Department of International Health
                            Atlanta, GA

     9:50 a.m.              Questions and Answers

14
on Vaccine Research
                                         FINAL PROGRAM
    10:00 a.m.        Coffee Break                                                                   Stadium Ballroom

    10:30 a.m.        Poster Session                                                                 Stadium Ballroom

    11:45 a.m.        Charles Mérieux Award Luncheon                                                  Grand Ballroom
                      Honoring Kristin L. Nichol, M.D., Ph.D.
                      Professor of Medicine, University of Minnesota and
                      Chief of Medicine, VA Medical Center
                      Minneapolis, MN

Symposium 1:          Conjugate Vaccine Issues                                                        Grand Ballroom
                      Moderator:       Myron M. Levine, M.D., D.T.P.H.
                                       University of Maryland School of Medicine

    1:00 p.m.    3.   Avidity and Biological Activity of Antibodies Elicited by Pneumococcal, Hib,
                      and Meningococcal Conjugate Vaccines
                      David Goldblatt, M.D., Ph.D.
                      University College of London
                      London, United Kingdom

    1:25 p.m.         Questions and Answers

    1:30 p.m.    4.   Long-term Immunologic Memory: Insights from the UK Experience with Haemophilus
                      Influenzae Type b and Meningococcal C Conjugates
                      Elizabeth Miller, M.D.
                      Communicable Disease Surveillance Center
                      London, United Kingdom

    1:55 p.m.         Questions and Answers

    2:00 p.m.    5.   Results of the Pneumococcal Conjugate Vaccine Trial
                      Felicity Cutts, Ph.D.
                      World Health Organization
                      Geneva, Switzerland

    2:25 p.m.         Questions and Answers

    2:30 p.m.    6.   New Conjugate Vaccine to Prevent Anthrax
                      John Robbins, M.D.
                      National Institute of Child Health and Human Development, NIH
                      Bethesda, MD




                                                                                                                   15
     Eighth Annual Conference
                                              FINAL PROGRAM

 MONDAY, MAY 9, 2005 (CONTINUED)
     2:55 p.m.        Questions and Answers

     3:00 p.m.        Coffee Break                                                                   Stadium Ballroom


 Symposium 2:         Update on Vaccines Against Enteric            CME                               Grand Ballroom
                      and Oral Infections
                      Moderator:       Richard J. Duma, M.D., Ph.D.
                                       Halifax Medical Center

     3:30 p.m.   7.   New Rotavirus Vaccines
                      Duncan Steele, M.D.
                      World Health Organization
                      Geneva, Switzerland

     3:55 p.m.        Questions and Answers

     4:00 p.m.   8.   Progress in Vaccines Against Norwalk Virus
                      Robert L. Atmar, M.D.
                      Baylor College of Medicine
                      Houston, TX

     4:25 p.m.        Questions and Answers

     4:30 p.m.   9.   Immunology and Potential Vaccine Prevention of Clostridium difficile Colitis
                      Karen L. Kotloff, M.D.
                      University of Maryland School of Medicine
                      Baltimore, MD

     4:55 p.m.        Questions and Answers

     5:00 p.m.   10. Update on Microbiology, Immunology and Vaccine Prevention of Dental Caries
                     Suzanne M. Michalek, Ph.D.
                     University of Alabama at Birmingham
                     Birmingham, AL

     5:25 p.m.        Questions and Answers

     5:30 p.m.        Adjournment and Poster Reception                                               Stadium Ballroom




16
on Vaccine Research
                                             FINAL PROGRAM

TUESDAY, MAY 10, 2005

    7:00 a.m.–5:00 p.m. Registration                                                             Grand Ballroom Foyer

    7:00 a.m.–7:45 a.m. Meet the Experts Breakfast Session                                             Patapsco Room

    7:30 a.m.            Continental Breakfast                                                   Grand Ballroom Foyer

Symposium 3:             Influenza and Vaccines for Emergency Pandemics            CME                Grand Ballroom
                         Moderator:        Peter L. Nara, D.V.M., Ph.D.
                                           Biological Mimetics, Inc

    8:00 a.m.      11. Perspective of Vaccine Manufacturers
                       Giuseppe Del Giudice, M.D.
                       Chiron Vaccines
                       Siena, Italy

    8:25 a.m.            Questions and Answers

    8:30 a.m.      12. Vaccines Against SARS: Where Do We Stand?
                       Albert D.M.E. Osterhaus, D.V.M., Ph.D.
                       Erasmus Medical College
                       Rotterdam, Netherlands

    8:55 a.m.            Questions and Answers

    9:00 a.m.      13. Vaccines for Prevention, Management, and Eradication of Avian Influenza
                       David Swayne, M.D.
                       United States Department of Agriculture
                       Athens, GA

    9:25 a.m.            Questions and Answers

    9:30 a.m.      14. West Nile: An Overview of the Epidemic in North America
                       Alan D.T. Barrett, Ph.D.
                       University of Texas Medical Branch
                       Galveston, TX

    9:55 a.m.            Questions and Answers

    10:00 a.m.     15. Vaccination for Emergency and Emerging Animal Health Events
                       Richard E. Hill, Jr., D.V.M.
                       United States Department of Agriculture
                       Washington, DC
                                                                                                                  17
     Eighth Annual Conference
                                                 FINAL PROGRAM

 TUESDAY, MAY 10, 2005 (CONTINUED)
      10:25 a.m.         Questions and Answers

      10:30 a.m.         Coffee Break/Exhibits                                                      Stadium Ballroom

 Submitted
 Presentations 1:        New Vaccines and Novel Vaccine Use            CME           Grand Ballroom East/Salons A,B,C
 (Concurrent Session)    Moderator:       Giuseppe Del Giudice, M.D.
                                          Chiron Vaccines

      11:00 a.m.    S1   Lipotechoic Acid Conjugate Vaccine for Staphylococcus
                         A. Lees, J. KoKai-kun, A. LopezAcosta, J. Acevedo, J. Mond
                         Biosynexus Inc, Gaithersburg, MD

      11:15 a.m.    S2   Adult Formulation Tetanus and Diphtheria Toxoids with Acellular Pertussis
                         Vaccine (Tdap) has Comparable Immunogenicity but Less Reactogenicity
                         than DTaP-IPV for the Pre-school, Fifth-dose Booster
                         J. M. Langley1, S. A. Halperin1, E. Mills2, A. Tomovici2, R. Guasparini3, G. Predy4,
                         B. Law5, F. Diaz-Mitoma6, P. Whitsitt7, B. Tapiero8, M. Dionne9
                         1Dalhousie University, Halifax, NS, CANADA, 2Sanofi-Pasteur, Toronto, ON, CANADA,
                         3TASC Research, Surrey, BC, CANADA, 4Capital-Health, Edmonton, AB, CANADA,
                         5Univ-Manitoba, Winnipeg, MB, CANADA, 6CHEO, Ottawa, ON, CANADA,
                         7Paradigm Clin Trials, Oshawa, ON, CANADA, 8Hop-Ste-Justine, Montreal, PQ,

                         CANADA, 9CHUQ, Beauport, PQ, CANADA.

      11:30 a.m.    S3   An Antigen-antibody-complex- based Therapeutic Vaccine for Chronic Hepatitis B Patients
                         Y. Wen1, D. Xu2, Z. Yuan1, K. Zhao3
                         1Department of Medical Molecular Virology, Shanghai Medical College, Fudan University,

                         Shanghai, CHINA, 2Dept.Infectious Diseases, Di Tan Hospital, Beijing, CHINA,
                         3Beijing Institute of Biological Product, Beijingi, CHINA.


      11:45 a.m.    S4   Different Immune Response after Sequential Use of Pneumococcal
                         Polysaccharide and Pneumococcal Conjugate Vaccine
                         A. de Roux1, B. Schmoele-Thoma2, N. Ahlers2, W. Gruber3, G. Siber3,
                         D. Sikkema3, T. Welte4, H. Lode1
                         1Heliosklinik Emil-von-Behring, Berlin, GERMANY, 2Wyeth, Muenster, GERMANY,
                         3Wyeth, Pearl River, NY, 4University Hannover, Hannover, GERMANY.


      12:00 p.m.    S5   Induction of Therapeutic Antitumor Immunity via Chemokine Receptor
                         Mediated Antigen Cross-presentation
                         A. Biragyn, D. Baatar, R. Schiavo
                         Laboratory of Immunology, GRC, National Institute on Aging, Baltimore, MD.

18
on Vaccine Research
                                           FINAL PROGRAM
     12:15 p.m.    S6   Directed Molecular Evolution Creates HIV-1 Novel gp120 Variants That Induce Broadly
                        Neutralizing Antibodies in Rabbits
                        L. Xu, X. Du, R. Whalen
                        Infectious Diseases, Maxygen, Inc., Redwood City, CA.

     12:30 p.m.         Lunch (on your own)

Submitted
Presentations 2:        Vaccines for Enteric and Tropical Pathogens           CME      Grand Ballroom West/Salons D,E,F
(Concurrent Session)    Moderator:     Carol J. Baker, M.D.
                                       Baylor College of Medicine

     11:00 a.m.    S7   The Human Hookworm Vaccine Initiative (HHVI): Progress in the Product Development
                        and Testing of the Na-ASP-2 Hookworm Vaccine
                        M. E. Bottazzi1, J. Bethony1, S. Brooker2, G. Goud1, A. Loukas3, S. Mendez1,
                        B. Zhan1, K. Stoever4, P. Hotez1
                        1Microbiology and Tropical Medicine, The George Washington University,

                        Washington, DC, 2London School of Hygiene and Tropical Medicine, London,
                        UNITED KINGDOM, 3Queensland Institute of Medical Research, Brisbane,
                        AUSTRALIA, 4Human Hookworm Vaccine Initiative, Sabin Vaccine Institute,
                        Washington, DC.

     11:15 a.m.    S8   The Human Hookworm Vaccine Initiative (HHVI): Novel Design and Statistical Considerations
                        to Estimate the Efficacy of a Helminth Vaccine in Field Trials in Endemic Region:
                        Phase 2b Studies for a Human Hookworm Vaccine
                        J Bethony1, S Brooker2, N Alexander2, S Geiger1, L Rodrigues3, ME Bottazzi1,
                        K Stoever3, P Hotez1
                        1The George Washington University, USA, 2London School of Hygiene and

                        Tropical Medicine, UK, 3Sabin Vaccine Institute, USA

     11:30 a.m.    S9   Safety and Immunogenicity of Vaccines against Cholera and Enterotoxigenic Escherichia coli
                        Diarrhea in Children In Bangladesh: Problems Encountered and Milestones Achieved
                        F. Qadri, D. A. Sack
                        Laboratory Sciences Division, ICDDR,B, Dhaka, BANGLADESH,

     11:45 a.m.    S10 Mass Vaccination Against Shigellosis: First Experience of Routine Immunization Against
                       Shigella sonnei Infection
                       R. P. Chuprinina1, L. I. Pavlova1, T. I. Frolushkina1, A. V. Protodiakonov1,
                       T. V. Gantcho2, M. E. Golovina2, V. I. Shmigol2, S. I. Elkina2, I. Y. Kurbatova2,
                       V. L. Lvov2, P. G. Aparin2
                       1Carbohydrate Vaccines, Ministry of Health Russia, Moscow, RUSSIAN FEDERATION,
                       2Carbohydrate Vaccines, NRC-Institute of Immunology, Moscow, RUSSIAN
                       FEDERATION.

                                                                                                                      19
     Eighth Annual Conference
                                               FINAL PROGRAM

 TUESDAY, MAY 10, 2005 (CONTINUED)
     12:00 p.m.   S11 Randomized, Double-blind Phase I Study to Assess the Safety, Tolerability, Immunogenicity,
                      Dose Response, and Transmissibility of CVD 1208S, a guaBA, sen, and Set Deleted, Live,
                      Oral Shigella flexneri 2a Soy Based Vaccine
                      K. L. Kotloff1, J. K. Simon1, M. Pasetti1, J. P. Nataro1, M. B. Sztein1,
                      S. S. Wasserman2, W. C. Blackwelder1, E. M. Barry2, M. M. Levine1
                      1Pediatrics, University of Maryland, Baltimore, MD,
                      2Medicine, University of Maryland, Baltimore, MD.


     12:15 p.m.   S12 Phase 1 Study of the Safety and Immunogenicity of Amai-C1/Alhydrogel® Vaccine for
                      Plasmodium Falciparum Malaria in Semi-Immune Malian Adults
                      A. Dicko1, D. Diemert2, I. Sagara1, M. Sogoba1, M. Niambele1, M. Assadou1,
                      O. Guindo1, B. Kamate1, M. Baby1, M. Sissoko1, G. Mullen2, E. Malkin2,
                      M. Sissoko1, M. Thera1, A. Dolo1, C. Long2, D. Diallo1, L. Miller2, A. Saul2,
                      O. Doumbo1;
                      1MRTC/University of Bamako, Bamako, MALI, 2MVDB/NIAID, Rockville, MD.



     12:30 p.m.        Lunch (on your own)


 Symposium 4:          Concrete Proposals for Ensuring A Secure                      CME             Grand Ballroom
                       Supply of Vaccines in the U.S.
                       Moderator:       Bruce G. Weniger, M.D.
                                        Centers for Disease Control and Prevention

     1:30 p.m.    16. Ideas from the National Vaccine Advisory Committee, the Institute
                      of Medicine, and Academia
                      Jerome O. Klein, M.D.
                      Boston Medical Center
                      Boston, MA

     1:55 p.m.         Questions and Answers

     2:00 p.m.    17. Vaccine Supply: A Manufacturer’s Perspective on Current Challenges and Opportunities
                      David R. Johnson, M.D.
                      sanofi pasteur
                      Swiftwater, PA

     2:25 p.m.         Questions and Answers




20
on Vaccine Research
                                                   FINAL PROGRAM
      2:30 p.m.        18. A Consensus Agenda to Strengthen U.S. Vaccine Supply
                           John M. Clymer
                           Partnership for Prevention
                           Washington, DC

      2:55 p.m.              Questions and Answers

      3:00 p.m.              Coffee Break/Exhibits                                                        Stadium Ballroom

Symposium 5:                 Vaccinology of Neglected Diseases: Malaria* CME                               Grand Ballroom
                             Moderator:        N. Regina Rabinovich
                                               Bill & Melinda Gates Foundation

      3:30 p.m.        19. Progress in the Field of Malaria Vaccinology
                           Filip Dubovsky, M.D., M.P.H.
                           Malaria Vaccine Initiative
                           Bethesda, MD

      3:55 p.m.              Questions and Answers

      4:00 p.m.        20. Novel and Classical Strategies for Attenuated Malaria Vaccines
                           Stephan Kappe, Ph.D.
                           Seattle Biomedical Research Institute
                           Seattle, WA

      4:25 p.m.              Questions and Answers

      4:30 p.m.        21. The Pathway Forward for Malaria Recombinant Vaccine (RTS,S): Implications of Study Results
                           W. Ripley Ballou, M.D.
                           GlaxoSmithKline Biologicals
                           Rixensart, Belgium

      4:55 p.m.              Questions and Answers

      5:00 p.m.        22. Developing Adjuvants for Malaria Vaccines
                           Lt. Col. Donald Gray Heppner, M.D.
                           Walter Reed Army Institute of Research
                           Silver Spring, MD

      5:25 p.m               Questions and Answers

      5:30 p.m.              Adjournment

*This symposium was made possible through an educational grant from the Bill & Melinda Gates Foundation

                                                                                                                         21
     Eighth Annual Conference
                                                   FINAL PROGRAM

 TUESDAY, MAY 10, 2005 (CONTINUED)
     6:00 p.m.             Albert B. Sabin Vaccine Institute Reception                         Grand Ballroom Foyer

     7:00 p.m.             Presentation of the Albert B. Sabin Gold Medal                           Grand Ballroom




 WEDNESDAY, MAY 11, 2005

     7:00 a.m.–7:45 a.m. Meet the Experts Breakfast Session                                          Patapsco Room

     7:30 a.m.–12:00 p.m. Registration                                                         Grand Ballroom Foyer

     7:30 a.m.             Continental Breakfast/Exhibits                                         Stadium Ballroom


 Symposium 6:              Therapeutic Vaccines             CME                                     Grand Ballroom
                           Moderator:        Diane E. Griffin, M.D., Ph.D.
                                             Johns Hopkins Bloomberg School of Public Health

     8:00 a.m.      23. Human Papilloma Virus Therapeutic Vaccines
                        W. Martin Kast, Ph.D.
                        University of Southern California
                        Los Angeles, CA

     8:25 a.m.             Questions and Answers

     8:30 a.m.      24. Hepatitis C Therapeutic Vaccines
                        Michael Houghton, Ph.D.
                        Chiron Corporation
                        Emeryville, CA

     8:55 a.m.             Questions and Answers

     9:00 a.m.      25. Immunotherapy as a Treatment Possibility for Alzheimer’s Disease
                        Dale Schenk, Ph.D.
                        Elan Pharmaceuticals
                        South San Francisco, CA

     9:25 a.m.             Questions and Answers


22
on Vaccine Research
                                            FINAL PROGRAM
     9:30 a.m.     26. Vaccines for Type 1 Diabetes
                       Richard Insel, M.D.
                       Juvenile Diabetes Research Foundation International
                       New York, NY

     9:55 a.m.          Questions and Answers

     10:00 a.m.         Coffee Break/Exhibits                                                   Stadium Ballroom


Submitted
Presentations 3:        Vaccines for Epidemic Threats         CME                                 Grand Ballroom
(Concurrent Session)    Moderator:       Susan J. Rehm, M.D.                                     East/Salons A,B,C
                                         National Foundation for Infectious Diseases

     10:30 a.m.    S13 Oculo-respiratory Syndrome (ORS) and Other Adverse Events Following
                       Immunization (AEFIs) in Infants and Toddlers Given Influenza Vaccine
                       D. M. Skowronski1, S. A. Tweed1, V. Remple1, K. Pielak1, J. Daigneault2,
                       P. Daly3, G. Arsenault4, E. Galanis1, T. Tam5;
                       1BC Centre for Disease Control, Vancouver, BC, CANADA, 2Direction de Sante Publique,

                       Chicoutimi, PQ, CANADA, 3Vancouver Coastal Health Authority, Vancouver, BC,
                       CANADA, 4Fraser Health Authority, Surrey, BC, CANADA, 5Public Health Agency
                       of Canada, Ottawa, ON, CANADA.

     10:45 a.m.    S14 Improved Protective Antibody Responses Were Induced by Codon Optimized
                       DNA Vaccines Expressing Hemagglutinin Antigens of Influenza H1 and H3 Serotypes
                       S. Wang1, I. Mboujka1, J. Haran1, H. Cao1, X. Huang1, J. Taaffe2, A. Solórzano2,
                       A. García-Sastre2, S. Lu1;
                       1Department of Medicine, University of Massachusetts Medical School, Worcester, MA,
                       2Department of Microbiology, Mount Sinai School of Medicine, New York, NY.


     11:00 a.m.    S15 Protective Measures and Human Antibody Response to HPAI H7N3 in
                       British Columbia (BC), Canada
                       D. M. Skowronski1, Y. Li2, S. A. Tweed1, T. Tam3, M. Petric1, S. Berger1,
                       A. Larder4, N. Bastien2, A. King3, R. C. Brunham1;
                       1BC Centre for Disease Control, Vancouver, BC, CANADA, 2Public Health Agency of

                       Canada, Winnipeg, MB, CANADA, 3Public Health Agency of Canada, Ottawa, ON,
                       CANADA, 4Fraser Health, Abbotsford, BC, CANADA.




                                                                                                                23
     Eighth Annual Conference
                                            FINAL PROGRAM

 WEDNESDAY, MAY 11, 2005 (CONTINUED)
      11:15 a.m.    S16 T Cell Multi-Epitope Vaccine for Pandemic Influenza
                        J. Alexander1, B. Stewart1, P. Bilsel1, J. Katz2, M. Newman1;
                        1Epimmune, San Diego, CA, 2Centers for Disease Control and Prevention, Atlanta, GA.


      11:30 a.m.    S17 Immunization with Salmonella enterica serovar Typhi Ty21a Expressing Anthrax
                        Protective Antigen Protects Mice from an Anthrax Lethal Toxin Challenge
                        Y. Wu, M. Osorio, S. Bhattacharyya, M. D. Bray, R. Walker, D. J. Kopecko;
                        FDA-CBER, Bethesda, MD.

      11:45 a.m.    S18 Assessment of the Reactogenicity of Tdap in Children and Adolescents 7-19 Years of Age
                        by Interval Since Prior Tetanus and Diphtheria Toxoids Containing Vaccine
                        S.A. Halperin1, L. Sweet2, D. Baxendale1, A. Neatby2, P. Rykers1, B. Smith1,
                        M. Zelman2, D. Maus3, P. Lavigne3, M. Decker3
                        1Dalhousie University, Halifax, NS, CANADA, 2Department of Health and Social

                        Services, Charlottetown, PE, CANADA, 3Sanofi Pasteur, Toronto ON, CANADA,
                        and Swiftwater, PA, USA

      12:00 p.m.         Lunch (on your own)

 Submitted
 Presentations 4:        Innovations in Vaccine Design CME                             Grand Ballroom West/Salons D,E,F
 (Concurrent Session)    and Studies of Immune Response
                         Moderator:     Connie Schmaljohn, Ph.D.
                                        U.S. Army Medical Research Institute of Infectious Diseases

      10:30 a.m.    S19 Oral Vaccine Delivery by Salmonella Vaccine Vectors
                        M. E. Gahan1, D. E. Webster1, S. L. Wesselingh1, B. B. Finlay2, R. A. Strugnell3
                        1Macfarlane Burnet Institute & Department of Medicine, Monash University, Melbourne,

                        AUSTRALIA, 2Michael Smith Laboratories, University of British Columbia, Vancouver,
                        BC, CANADA, 3Department of Microbiology and Immunology, University of Melbourne,
                        Melbourne, AUSTRALIA.

      10:45 a.m.    S20 CpG Oligodeoxynucleotides Co-administered With the Microneme Protein MIC2 Protect
                        Against Eimeria Infections
                        R. A. Dalloul1, H. S. Lillehoj1, D. M. Klinman2, X. Ding1, W. Min1,
                        R. A. Heckert1, E. P. Lillehoj3
                        1Animal Parasitic Diseases Laboratory, USDA, Beltsville, MD, 2Section of Retroviral
                        Immunology, Center for Biologics Evaluation & Research, US FDA, Bethesda, MD,
                        3Department of Pediatrics, School of Medicine, University of Maryland, Baltimore, MD.




24
on Vaccine Research
                                         FINAL PROGRAM
   11:00 a.m.   S21 Immunogenicity of Combination DNA Vaccines for RVFV, TBEV, HTNV, and CCHFV
                    K.W. Spik, A. Shurtleff, A.K. McElroy, M.C. Guttieri, J. W. Hooper, and C. Schmaljohn
                    Virology Division, United States Army Medical Research Institute of Infectious Diseases,
                    Fort Detrick, Frederick, MD

   11:15 a.m.   S22 Genetic Influence of HLA Haplotypes on Immune Responses Following Measles-Mumps-Rubella
                    (MMR-II) Vaccination in Children
                    I. G. Ovsyannikova1, S. V. Pankratz2, R. M. Jacobson1, R. A. Vierkant2, G. A. Poland1
                    1Vaccine Research Group, Mayo Clinic College of Medicine, Rochester, MN,
                    2Health Science Research, Mayo Clinic College of Medicine, Rochester, MN.


   11:30 a.m.   S23 Correlations among Measles Virus-Specific Antibody, Lymphoproliferation and Th1/Th2
                    Cytokine Responses Following MMR-II Vaccination
                    N. Dhiman, I. G. Ovsyannikova, J. E. Ryan, R. M. Jacobson, R. A. Vierkant,
                    S. V. Pankratz, S. J. Jacobsen, G. A. Poland
                    Mayo Vaccine Research Group, Mayo Clinic College of Medicine, Rochester, MN

   11:45 a.m.   S24 Mumps Virus Vaccine Strain Urabe AM9: Identification of Nucleotide Changes Associated
                    with Variability in the Neurovirulent Phenotype
                    C. J. Sauder, S. A. Rubin, K. M. Vandenburgh, K. M. Carbone;
                    FDA/CBER, Bethesda, MD.

   12:00 p.m.        Lunch (on your own)


Symposium 7:         Vaccinology Impact of Recent Advances CME                                   Grand Ballroom
                     In Immunology
                     Moderator:       Paul-Henri Lambert, M.D.
                                      Centre Medical Universitaire

   1:00 p.m.    27. Limitations of B-cell Responses in Early Life
                    Claire-Anne Siegrist, M.D.
                    University of Geneva
                    Geneva, Switzerland

   1:25 p.m.         Questions and Answers

   1:30 p.m.    28   Recent Advances in Studies of B and T cell Responses Early in Life
                     James E. Crowe, Jr., M.D.
                     Vanderbilt University
                     Nashville, TN

   1:55 p.m.         Questions and Answers


                                                                                                              25
     Eighth Annual Conference
                                              FINAL PROGRAM

 WEDNESDAY, MAY 11, 2005 (CONTINUED)
     2:00 p.m.   29. Innate Imprinting and Inflammatory Lung Disease
                     Tracy Hussell, Ph.D.
                     Imperial College London
                     London, England

     2:25 p.m.        Questions and Answers

     2:30 p.m.   30. Interrogating and Exploiting Memory B Cells
                     Antonio Lanzavecchia, M.D.
                     Institute for Research in Biomedicine.
                     Bellinzona, Switzerland

     2:55 p.m.        Questions and Answers

     3:00 p.m.        Coffee Break/Exhibits                                                       Stadium Ballroom


 Symposium 8:    Multi-Agent and Chimeric Vaccines          CME                                    Grand Ballroom
                 Moderator:            Hana Golding, Ph.D.
                                       Center for Biologics Evaluation and Research/FDA

     3:30 p.m.   31. The Use of MVA as a Vaccine Delivery Vector to Elicit Protective Immune
                     Responses Against Pathogens
                     Harriet L. Robinson, Ph.D.
                     Emory University
                     Atlanta, GA

     3:55 p.m.        Questions and Answers

     4:00 p.m.   32. Strategies for HIV Vaccine Development
                     John W. Shiver, Ph.D.
                     Merck and Company, Inc.
                     West Point, PA

     4:25 p.m.        Questions and Answers

     4:30 p.m.   33. Development of Novel Vaccine Candidates Using Directed Molecular Evolution
                     Christopher P. Locher, Ph.D.
                     Maxygen, Inc.
                     Redwood City, CA

     4:55 p.m.        Questions and Answers


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                                           FINAL PROGRAM
    5:00 p.m.     34. ChimeriVaxTh: A Novel Platform for Genetically Engineered Live Viral Vaccine
                      Thomas P. Monath, M.D.
                      Acambis, Inc.
                      Cambridge, MA

    5:25 p.m.          Questions and Answers

    5:30 p.m.          Adjournment/Participant Evaluation


Poster Session         (Monday, May 9, 10:30 a.m. – 11:30 a.m., Stadium Ballroom; Posters will be
                       on display throughout the day on Monday and will conclude with the Poster
                       Reception at 5:30 p.m.)

Poster Group 1:        Adjuvants and Immunomodulators

                  P1   Immune Responses Induced by Intranasal Immunization with Influenza
                       H3N2-anti-H3N2 complex in Mice
                       X. Yao, Y. Wen
                       Fudan University, Shanghai, CHINA.

                  P2   Flagellin is an Effective Mucosal Adjuvant in the Development of a Protective Immune
                       Response Against Yersinia pestis
                       A. N. Honko, S. B. Mizel
                       Microbiology and Immunology, Wake Forest University School of Medicine,
                       Winston-Salem, NC.

                  P3   Induction of Active Immune Suppression by Co-immunization of DNA-protein Vaccines
                       B. Wang, H. Jin, Y. Kang
                       State Key Lab for Agro-Biotechnology, China Agricultural University,
                       Beijing, CHINA.

                  P4   Aluminum Phosphate is an Active Adjuvant for CRM197 Pneumococcal Conjugate Vaccine
                       (PnC) in Infants
                       S. Lockhart1, W. Watson1, P. Fletcher2, A. Leeper3, S. Edwards4, M. McCaughey5,
                       A. Dunning1, D. Sikkema1, G. Siber1
                       1Wyeth Research, Pearl River, NY, 2Woolwell Surgery, Plymouth, UNITED KINGDOM,
                       3Grove Surgery, Thetford, UNITED KINGDOM, 4North Cardiff Medical Centre,

                       Cardiff, UNITED KINGDOM, 5Health Centre, Randalstown, UNITED KINGDOM.


                  P5   PyNTTTTGT Oligonucleotide IMT504 is a Potent Vaccine Adjuvant
                       A. D. Montaner1, F. Elias2, J. M. Rodriguez2, J. Flo2, R. Lopez2, J. Zorzopulos1
                       1Instituto de Investigaciones Biomédicas, Fundación Pablo Cassará., Buenos Aires,

                       ARGENTINA, 2Immunotech S.A., Buenos Aires, ARGENTINA.
                                                                                                              27
     Eighth Annual Conference
                                           FINAL PROGRAM

 POSTER SESSIONS (CONTINUED)

 Poster Group 2:        Antigen Presentation and Processing

                   P6   Novel Peptide Nanoparticles: A Platform for Vaccine Design
                        D. Tropel1, A. C. Tissot2, C. Schellekens2, S. K. Raman1, A. Graff1, G. Machaidze1,
                        M. F. Bachmann2, P. Burkhard3
                        1M.E Mueller Institute, Biozentrum, Basel, SWITZERLAND, 2Cytos Biotechnology,

                        Schlieren, SWITZERLAND, 3The Institute of Materials Science, University of
                        Connecticut, Storrs, CT

                   P7   Native Display of An HIV Tat Peptide on the Surface of Human Ferritin
                        C. Li, E. Soistman, D. C. Carter
                        New Century Pharmaceuticals, Inc, Huntsville, AL.

 Poster Group 3:        Assessing Immunologic Response and Disease Protection

                   P8   Protection against hepatitis B carriage following infant vaccination may fall with age
                        M. E. Mendy, M. A. B. van der Sande, P. Waight, P. Rayco-Solon, P. Hutt, T. Fulford,
                        C. Doherty, S. McConkey, D. Jefferies, A. Hall, H. Whittle
                        Viral Disease Programme, Medical Research Council, Banjul, GAMBIA.

                   P9   T cell responses to hepatitis B vaccine
                        M. S. Hayney, N. A. Wiegert
                        University of Wisconsin School of Pharmacy, Madison, WI.

                   P10 T cell responses following hepatitis A Immunizaton
                       M. S. Hayney, N. A. Wiegert;
                       University of Wisconsin School of Pharmacy, Madison, WI.

                   P11 Impact of a School Based Hepatitis B Immunization Program in a Low Endemic Area
                       V. Gilca1, B. Duval2, N. Boulianne2, R. Dion2, G. D. Serres2
                       1Centre de recherche du Centre Hospitalier Universitaire de Québec, Quebec, PQ,

                       CANADA, 2Institut National de Santé Publique du Québec, Quebec, PQ, CANADA,
                       2Laval University, Quebec, PQ, CANADA.



                   P12 Antibody Responses to Vaccinia Membrane Proteins Following Smallpox Vaccination
                       S. Lawrence1, K. Lottenbach2, F. Newman2, M. Buller2, C. Bellone2, S. Koehm2,
                       S. Stanley, Jr.1, R. Belshe2, S. Frey2
                       1Washington University, St. Louis, MO, 2Saint Louis University, St. Louis, MO




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                  P13 Serum Neopterin for Early Assessment of Severity of Severe Acute Respiratory Syndrome
                      J. W. Y. Choi
                      Department of Microbiology, The University of Hong Kong, Pokfulam, HONG
                      KONG SPECIAL ADMINISTRATIVE REGION OF CHINA

                  P14 Determining Avidity for Anti-polysaccharide Antibodies
                      S. Harris, J. Tam, P. Fernsten
                      Vaccines Research, Wyeth, Pearl River, NY.

                  P15 Quantitation of Human Serum Immunoglobulin G Against O-Acetyl Positive and O-Acetyl
                      Negative Serogroup W135 Meningococcal Capsular Polysaccharide
                      P. C. Giardina1, E. Longworth2, R. Borrow2, P. Fernsten1
                      1Applied Immunology and Microbiology, Wyeth, Pearl River, NY, 2Meningococcal
                      Reference Unit, Manchester Medical Microbiology Partnership, Health Protection
                      Agency, Manchester, UNITED KINGDOM.

                  P16 Evaluating the Influences of Glycosylation on the Immunogenicity of the Ebola Virus
                      Glycoprotein
                      W. E. Dowling1, R. J. Hogan2, E. Thompson3, J. Paragas1, G. Bush1, J. Smith1,
                      W. Capps1, L. Grey1, C. Badger1, C. S. Schmaljohn1
                      1Virology, USAMRIID, Fort Detrick, MD, 2Infectous Diseases, University of Georgia,

                      Athens, GA, 3CBER, FDA, Rockville, MD.

Poster Group 4:        Basic Science

                  P17 The Establishment of a Restriction Assorted Fragments Expression (RAFE) System
                      for Vaccine Development of HIV-1B Subtype
                      R. Shi1, W. Zheng2, J. Liu1, L. Li1, W. Ma1
                      1Institute of Molecular Biology, NanFang Medical University, Guangzhou, CHINA,
                      2South China Genomics Research Center, Guangzhou, CHINA.


                  P18 Toll-like Receptor 4 Plays Role in Activating Dendritic Cells by Necrotic Cells
                      C. Kang, J. Choi, S. Lee, H. Moon, S. Seong
                      Microbiology and Immunoogy, Seoul National University College of Medicine, Seoul,
                      REPUBLIC OF KOREA

                  P19 Construction of Recombinant BCG based HIV-1 Epitope Delivery System and Evaluation
                      of its Immunogenicity in a Murine Model
                      A. Vivekanandhan, N. Sujatha, P. Narayanan
                      Immunology, Tuberculosis Research Centre, Chennai, INDIA




                                                                                                              29
     Eighth Annual Conference
                                            FINAL PROGRAM

 POSTER SESSIONS (CONTINUED)
                   P20 Extending the Capsid Deletion Approach for Flavivirus Vaccine Development to the N-terminal
                       Part of the Protein
                       R. M. Kofler, C. W. Mandl
                       Clinical Institute of Virology, Medical University of Vienna, Vienna, AUSTRIA.

                   P21 Serotypes, Virulence Genes, and PFGE Patterns of Escherichia Coli Strains Isolated from
                       Piglets with Diarrhea in Slovakia
                       H. Vu Khac
                       Department of Bacteriology, Central Vietnam Veterinary Institute, Nha trang City,
                       VIETNAM.

                   P22 Phase 2 & 3 Vaccine Research Agenda in the Kintampo District of Ghana.
                       S. Owusu-Agyei
                       Ministry of Health, Kintampo Health Research Centre, Kintampo, GHANA.

                   P23 A Multiplex Real-Time PCR Assay with An Internal Control for Quantitative Detection of
                       Streptococcus pneumoniae
                       A. Hu, F. Li, P. Zhao, J. S. Tam, R. Rappaport, S. Cheng
                       Wyeth, Pearl River, NY.

                   P24 Cloning and Characterization of the Polysaccharide Biosynthetic Genes for Shigella
                       dysenteriae serotype 1 into Salmonella enterica serovar Typhi Ty21a
                       D. Xu1, J. O. Cisar2, D. J. Kopecko1
                       1FDA-CBER, Bethesda, MD, 2NIH-NIDCR, Bethesda, MD.



 Poster Group 5:        Clinical Studies & Field Trials (e.g., Phase 1,2, or 3 studies)

                   P25 Pneumococcal Disease and Influenza Vaccination Acceptance Among Health Care Workers
                       J. Wallenfels1, J. Rames2
                       1Ministry of Health of the Czech Republic, Praha, CZECH REPUBLIC, 2Institute of
                       Hygiene and Epidemiology, First Faculty of Medicine, Charles University in Prague, Praha,
                       CZECH REPUBLIC.

                   P26 Burden of Invasive Disease caused by Haemophilus influenzae Type b and Streptococcus
                       pneumoniae Among Infants in Bamako, Mali
                       S. O. Sow1, J. Campbell2, M. Tapia2, S. Diallo3, K. Kotloff2, M. Levine2
                       1Centre pour le Developpement des Vaccins, Bamako, MALI, 2University of Maryland

                       School of Medicine, Center for Vaccine Development, Baltimore, MD, 3Clinical
                       Bacteriology Laboratory and the Pediatric Service, Gabriel Touré Hospital, Bamako, MALI.

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   P27 Standardized Informed Consent for Low-literacy Audiences in African Research Environment
       B. E. Bekan
       Projet San Francisco, Kigali, RWANDA.

   P28 Compatibility of Co-administered 7-valent Pneumococcal Conjugate, DTaP.IPV/PRP-T Hib and
       Hepatitis B Vaccines in Infants
       D. W. Scheifele1, S. Halperin2, B. Smith2, K. Meloff3, D. Duarte-Monteiro3
       1University of British Columbia, Vancouver, BC, CANADA, 2Dalhousie University,

       Halifax, NS, CANADA, 3Wyeth Pharmaceuticals, Toronto, ON, CANADA.

   P29 Research Subject Satisfaction Assessment: A Missing Element of "Good Clinical Practices"
       C. LaJeunesse, A. Kallos, K. Marty, M. Mozel, D. W. Scheifele
       Vaccine Evaluation Center, University of British Columbia, Vancouver, BC, CANADA.

   P30 Comparison of the Safety and Immunogenicity of Simultaneous or Sequential Administration
        of an Adult Formulation Tdap Vaccine and Influenza Vaccine
       S. McNeil1, F. Noya2, M. Dionne3, G. Predy4, W. Meekison5, C. Ojah6, S. Ferro7,
       E. Mills7, J. Langley1, S. Halperin1
       1Dalhousie University, Halifax, NS, CANADA, 2Montreal Children's Hospital, Montreal,

       PQ, CANADA, 3INSPQ, Quebec City, PQ, CANADA, 4Capital-Health, Edmonton, AB,
       CANADA, 5Westcoast Clinical Research, Vancouver, BC, CANADA, 6Saint John Regional
       Hospital, Saint John, NB, CANADA, 7Sanofi-Pasteur, Toronto, ON, CANADA.

   P31 Measurement of Tetanus Antitoxin in Oral Fluid: A Novel Method to Evaluate Vaccination
       Programs
       M. D. Tapia1, L. Cuberos1, S. O. Sow2, M. N. Doumbia2, M. Bagayogo2,
       M. Pasetti1, K. Kotloff1, M. Levine1
       1University of Maryland School of Medicine, Baltimore, MD, 2Centre pour le
       Developpement des Vaccins - Mali, Bamako, MALI.

   P32 Studies on a Live Oral Attenuated Cholera Vaccine, Peru-15 in Bangladesh
       F. Qadri1, M. I. Chowdhury1, M. A. Salam1, S. M. Faruque1, T. Ahmed1, Y. A.
       Begum1, A. Saha1, L. V. Seidlein2, R. F. Breiman1, J. J. Mekalanos3, J. D. Clemens2,
       K. P. Killeen4, D. A. Sack1
       1ICDDR,B: Centre for Health and Population Research, Dhaka, BANGLADESH,
       2International Vaccine Institute, Seoul, DEMOCRATIC PEOPLE'S REPUBLIC OF

       KOREA, 3Harvard Medical School, Boston, MA, 4AVANT Immunotherapeutics,
       Needham, MA.




                                                                                                  31
     Eighth Annual Conference
                                            FINAL PROGRAM

POSTER SESSIONS (CONTINUED)

Poster Group 6:        Combination Vaccines

                  P33 A Novel Combination DNA and Inactivated Rabies Virus Vaccine
                      P. N. Rangarajan1, V. A. Srinivasan2
                      1Indian Institute of Science, Bangalore, INDIA, 2Indian Immunologicals
                      Limited, Hyderabad, INDIA.

                  P34 Minicircle DNA Immobilized in Bacterial Ghost: A Novel Non-living Bacterial DNA-vaccine
                      Carrier System
                      C. Azimpour Tabrizi1, W. Jechlinger2, P. Becker3, T. Ebensen3, C. Guzman3,
                      W. Lubitz1
                      1Microbiology and Genetic, Vienna, AUSTRIA, 2Inst. Bacteriology, Mycology and

                      Hygiene, Vienna, AUSTRIA, 3German Research Centre for Biotechnology, Braunschweig,
                      GERMANY.

                  P35 Multiple DNA Vaccine Plasmids Protect Mice from Acute Pulmonary Infection of Pseudomonas
                      aeruginosa
                      S. Saha1, F. Takeshita1, S. Sasaki1, T. Matsuda1, T. Matsumoto2, K. Yamaguchi2,
                      K. Okuda1
                      1Yokohama City University Graduate School of Medicine, Yokohama, JAPAN,
                      2Toho University School of Medicine, Tokyo, JAPAN.



                  P36 Infanrix™-IPV-Hib (GSK) is Safe and Immunogenic Compared to Pentacel™ (Sanofi Pasteur)
                      As a 4th Dose in 15-20 Month Olds
                      S. A. Halperin1, B. Tapiero2, B. Law3, B. Duval4, F. Diaz-Mitoma5, D. Elrick6
                      1Pediatrics, Dalhousie University, Halifax, NS, CANADA, 2Pediatrics, Ste Justine

                      Hospital, University of Montreal, Montreal, PQ, CANADA, 3Pediatrics, University of
                      Manitoba, Winnipeg, MB, CANADA, 4Institut National de Santé Publique, Quebec City,
                      PQ, CANADA, 5Pediatrics, Children's Hospital of Eastern Ontario, Ottawa, ON,
                      CANADA, 6GlaxoSmithKline, Inc, Mississauga, ON, CANADA.

Poster Group 7:        New Vaccines for Common Pathogens

                  P37 Immunization with Recombinant Adenovirus Synthesizing Secretory form of Japanese
                      Encephalitis Virus Envelope Protein Protects Adenovirus-Exposed Mice Against Lethal
                      Encephalitis
                      S. Vrati
                      National Institute of Immunology, New delhi, INDIA.



32
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                                         FINAL PROGRAM
                  P38 A Novel Live Adenovirus Vaccine Vector Prototype: High-level Antigen Production from the
                      Adenoviral Major Late Transcriptional Unit
                      M. G. Berg1, B. Falgout2, G. W. Ketner1
                      1Molecular Microbiology and Immunology, Johns Hopkins University, Baltimore, MD,
                      2CBER, Food & Drug Administration, Bethesda, MD.


                  P39 Construction of Live Attenuated Shigella Vaccine Candidates using Recombineering
                      R. Ranallo, S. Barnoy, S. Thakkar, M. Venkatesan
                      Enteric Infections, WRAIR, Silver Spring, MD.

                  P40 Oral Immunization of Dogs with Baits Containing the Recombinant Rabies Virus Glycoprotein/
                      Nucleoprotein-Canine Adenovirus Type 2
                      R. Hu, S. Zhang, H. li
                      Veterinary Institute, Academy of Military Medical Science, Changchun, CHINA.

                  P41 Immunological Properties of Conjugates Prepared from Pathogenic Candida Surface
                      Antigens: Potential Vaccines
                      S. Bystricky
                      Institute of Chemistry SAV, Bratislava, SLOVAKIA.

                  P42 A Novel Subunit Vaccine Protects Mice Against Systemic Disease and Intestinal Colonization
                      by Salmonella enterica
                      L. Wonderling1, D. Straub2, D. Emery2
                      1Syntiron, Saint Paul, MN, 2Epitopix, Willmar, MN.


                  P43 Partial Protection of Mice after DNA Vaccination Against Staphylococcus aureus Infection.
                      M. C. Gaudreau1, P. Lacasse2, B. G. Talbot1
                      1Biologie, University of Sherbrooke, Sherbrooke, PQ, CANADA, 2Agriculture and
                      Agri-Food Canada, Lennoxville, PQ, CANADA.

Poster Group 8:        Novel Antigens

                  P44 Strong B- and T-cell Response after Protein, DNA, and DNA Prime/protein Boost
                      Immunisation with HBV Cores Carrying HBV PreS1 Sequences
                      D. Skrastina, I. Sominskaya
                      Protein Engineering, Biomedical Research and Study Centre, University of Latvia, Riga,
                      LATVIA.

                  P45 Genetic Polymorphism and Positive Selection in a ‘Concealed’ Gut Potential Vaccine Antigen
                      from Rhipicephalus appendiculatus.
                      L. M. Kamau1, R. Skilton2, T. Musoke2, D. Wasawo2, J. Rowlands2, R. Bishop2
                      1Kenyatta University & International Livestock Research Institute (ILRI), Nairobi,

                      KENYA, 2International Livestock Research Institute (ILRI), Nairobi, KENYA.

                                                                                                                  33
     Eighth Annual Conference
                                            FINAL PROGRAM

POSTER SESSIONS (CONTINUED)
                  P46 A Recombinant 63-kilodalton Form of Bacillus anthracis Protective Antigen Produced in the
                      Yeast Saccharomyces cerevisiae Provides Protection in Two Inhalational Challenge Models of
                      Anthrax Infection.
                      R. W. Hepler1, R. Kelly1, T. B. McNeely1, H. Fan1, M. C. Losada1, H. A. George1,
                      A. Woods1, L. D. Cope1, A. Bansal1, J. C. Cook1, G. Zang1, S. L. Cohen1, X. Wei1,
                      P. M. Keller1, E. K. Leffel2, J. G. Joyce1, M. L. M. Pitt2, L. D. Schultz1,
                      K. U. Jansen1, M. Kurtz1
                      1Merck Research Labs, West Point, PA, 2US Army Medical Research Institute of Infectious
                      Diseases, Fort Detrick, MD.

                  P47 A Recombinant Leishmania Antigen Related to the Silent Information Regulatory 2 (SIR2)
                      Protein Family Induces a B cell Activation and Antibody Specific Immune Response
                      R. Silvestre1, A. Cordeiro-da-Silva1, A. Ouaissi2
                      1Faculdade Farmácia and I.B.M.C. of Universidade Porto, Porto, PORTUGAL,
                      2Institut de Recherche pour le Développement, UR008, Montpellier, FRANCE.



                  P48 DNA Vaccine Expressing D8L of Vaccinia Virus Enhanced the Efficacy of Multi-gene Smallpox
                      DNA Vaccine Formulations
                      P. V. Sakhatskyy, S. Wang, T. Chou, S. Lu
                      University of Massachusetts Medical School, Worcester, MA.

Poster Group 9:        Preclinical Studies (e.g. laboratory animal)

                  P49 An Intranasal, Protollin™-RSV Subunit Vaccine Induces Mucosal IgA, Serum Neutralizing
                      Antibodies and a Type-1 Cytokine-biased Response by Spleen and Lung Mononuclear Cells
                      in Mice.
                      S. L. Cyr1, T. Jones2, I. Stoica-Popescu2, S. Chabot1, D. S. Burt2, B. J. Ward1
                      1Microbiology and Immunology, McGill University, Montreal, PQ, CANADA,
                      2ID Biomedical, Laval, PQ, CANADA.



                  P50 Prevention of Serogroup A, C and W135 Meningococcal Disease in the Meningitis Belt of
                      Africa by Targeting Outer Membrane Proteins
                      E. Rosenqvist, G. Norheim, E. Fritzsønn, T. Tangen, P. Kristiansen, D. A. Caugant,
                      A. Aase, E. A. Høiby, I. S. Aaberge
                      Division for Infectious Disease Control, Norwegian Institute of Public Health, Oslo,
                      NORWAY.




34
on Vaccine Research
                                          FINAL PROGRAM
                   P51 Development and Use of the Outer Membrane Vesicle Concept for Vaccines Against
                       Meningococcal Group B Disease
                       E. Rosenqvist1, G. Norheim1, L. Meyer Næss1, P. Kristiansen1, P. Costantino2,
                       E. Wedege1, D. A. Caugant1, B. Feiring1, I. S. Aaberge1, R. Rappuoli3, J. Holst1
                       1Division for Infectious Disease Control, Norwegian Insitute of Public Health, Oslo,

                       NORWAY, 2Chiron Vaccines S.r.l., Siena, ITALY, 3Chiron Vaccine S.r.l., Siena, ITALY.

                   P52 Reducing the Cost of Manufacturing Conjugate Vaccines: Effective Alternatives to Gel
                       Filtration
                       A. Lees, D. E. Shafer
                       Biosynexus Inc, Gaithersburg, MD.

                   P53 Aminooxy Reagents and Oxime Chemistry for the Preparation of Conjugate Vaccines
                       A. Lees, A. LopezAcosta
                       Biosynexus Inc, Gaithersburg, MD.

                   P54 Development of HIV-1 Subtype C Vaccine Candidates
                       P. Seth
                       Microbiology, All India Institute of Medical Sciences, New Delhi, INDIA.

                   P55 Enhancement of Cell-mediated Immunity in Mice by the Model of a Whole HIV-1 Gag in Live
                       Mycobacterium bovis BCG.
                       D. Promkhatkaew
                       Department Of Medical Sciences, Nonthaburi, THAILAND.

                   P56 Preclinical Development of Yeast-Based Immunotherapy for Chronic Hepatitis C Virus Infection
                       A. A. Haller, T. King, Y. Lu, C. Kemmler, D. Bellgrau, G. Gordon, D. Apelian,
                       A. Franzusoff, T. C. Rodell, R. C. Duke
                       GlobeImmune Inc., Aurora, CO.

Poster Group 10:        Product Development

                   P57 Analytical Challenges for Novel Vaccine Formulations
                       E. Hartwell, S. D. Sen, B. J. Roser
                       Cambridge Biostability Ltd, Cambridge, UNITED KINGDOM.

                   P58 Production and Control of a Brazilian Meningococcal C Conjugate Vaccine
                       I. A. Silveria
                       Departamento de Desenvolvimento Tecnológico, Fundação Oswaldo Cruz / Biomanguinhos,
                       Rio de Janeiro, BRAZIL.



                                                                                                                35
     Eighth Annual Conference
                                             FINAL PROGRAM

POSTER SESSIONS (CONTINUED)
                   P59 Production and Control of a Brazilian Meningococcal B Vaccine
                       I. A. Silveria
                       Departamento de Desenvolvimento Tecnológico, Fundação Oswaldo Cruz / Biomanguinhos,
                       Rio de Janeiro, BRAZIL.

Poster Group 11:        Routes of Antigen Administration and Vaccine Safety

                   P60 Needle-Free Delivery of Antigens to Ultrasound Pre-treated Skin Demonstrated in a
                       Feasibility Clinical Trial
                       D. H. Libraty1, S. P. Barman2
                       1Center for Infectious Diseases & Vaccine Research, University of Massachusetts Medical

                       School, Worcester, MA, 2Transdermal Drug Delivery , Vaccines, Sontra Medical, Franklin,
                       MA.

                   P61 Anaphylaxis Following Recombinant Hepatitis B Vaccines in Yeast-Sensitive Individuals:
                       Reports to VAERS
                       L. DiMiceli1, V. Pool1, S. V. Shadomy2, J. Iskander1
                       1CDC/National Immunization Program, Atlanta, GA, 2CDC/National Center for
                       Infectious Diseases, Atlanta, GA.

                   P62 Histopathology Analysis of Local Reactions in Mice following Injection of
                       Diphtheria-Tetanus-Acellular Pertussis (DTaP) vaccines
                       A. Honjo, T. Katsuta, S. Tateyama, C. Nagaoka, T. Tokutake, Y. Arimoto,
                       N. Nakajima, T. Goshima, T. Kato
                       St.Mariannna University School of Medicine, Kawasaki-si, JAPAN.

Poster Group 12:        Vaccines for New and Reemerging Pathogens and Vaccines for Tropical
                        and/or Exotic Pathogens

                   P63 CAP adsorbed rPA Nasal Vaccine as an Approach to Mucosal Immune Protection Against
                       Anthrax Infection
                       P. Nagappan1, J. Arroyo2, T. Morcol1, A. R. Mitchell1, L. Nerenbaum1,
                       S. Billingsley1, S. J. D. Bell1
                       1BioSante Pharmaceuticals, Inc., Smyrna, GA, 2DVC LLC a CSC Company, Frederick,
                       MD.

                   P64 Influenza Nucleoprotein Conjugated to Immunostimulatory DNA as a Potential Vaccine
                       Against Pandemic Influenza
                       T. dela Cruz1, D. Higgins1, G. Ott1, I. Mbawuike2, S. Tuck1, G. Van Nest1
                       1Dynavax Technologies, Berkeley, CA, 2Baylor College of Medicine, Houston, TX.


36
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                                          FINAL PROGRAM
                   P65 Development of SARS Vaccine Using Recombinant Vaccinia Virus Derived from LC16m8
                       M. Kitabatake1, F. Yasui2, S. Inoue3, K. Morita3, F. Murai4, M. Kidokoro5,
                       K. Mizuno6, H. Shida7, K. Matsushima1, M. Kohara2
                       1Univ. Tokyo, Tokyo, JAPAN, 2The Tokyo Metro. Inst. Med. Sci., Tokyo, JAPAN,
                       3Inst. Tropical Med., Nagasaki Univ., Nagasaki, JAPAN, 4Post Genome Inst., Tokyo,

                       JAPAN, 5Natl. Inst. Infect. Dis., Tokyo, JAPAN, 6The Chemo-Sero-Therapeutic Res. Inst.,
                       Kumamoto, JAPAN, 7Inst. Gen. Med., Hokkaido Univ., Sapporo, JAPAN.

                   P66 A Novel Subunit Vaccine Protects Mice Against Yersinia Infection
                       L. Wonderling1, D. Straub2, D. Emery2
                       1Syntiron, Saint Paul, MN, 2Epitopix, Willmar, MN.



                   P67 Cysteine Proteinases Based Vaccines for L. major and L. infantum Infections
                       S. Rafati, T. Taheri, A. Zadeh Vakili, A. Nakhaee, F. Zahedifard, Y. Taslimi,
                       F. Doustdari
                       Immunology, Pasteur Institute of Iran, Tehran, IRAN (ISLAMIC REPUBLIC OF).

                   P68 Development of Attenuated Mutants as Potential Vaccine Candidates for Visceral
                       leishmaniasis
                       P. Salotra1, G. Sreenivas2, R. Singh1, A. Selvapandiyan3, R. Duncan3, H. L. Nakhasi3
                       1Institute of Pathology (ICMR), New Delhi, INDIA, 2Insitute of Pathology (ICMR),

                       New Delhi, INDIA, 3CBER, FDA, Bethesda, MD.

                   P69 Protection Studies with Candidate Schistosoma mansoni DNAVaccines
                       A. M. Karim1, N. El-Ghazali1, A. Medhat1, S. F. Ibrahim2
                       1Ain Shams Univ. Fac. of Science, Cairo, EGYPT, 2Cairo Univ. Fac. of Science, Cairo,
                       EGYPT.

                   P70 Protective Immunity of Single and Multiple Recombinant DNA or Protein Vaccines Against
                       Lymphatic Filariasis.
                       P. Kaliraj, Sr.1, S. Anand1, V. Murugan1, K. Kirithika2, M. Reddy2
                       1Anna University, Chennai, INDIA, 2MGIMS, Sevagram, INDIA.




Poster Group 13:        Veterinary Vaccines

                   P71 Enhancing Brucellosis Vaccines, Vaccine Delivery Systems and Surveillance Diagnostics for
                       Bison and Elk in the Greater Yellowstone Area
                       G. E. Plumb, Jr.1, B. Marsh2
                       1Yellowstone National Park, US National Park Service, Yellowstone National Park, WY,
                       2Board of Animal Health, State of Indiana, Indianapolis, IN.




                                                                                                                   37
     Eighth Annual Conference
                                           FINAL PROGRAM

POSTER SESSIONS (CONTINUED)
                P72 Canine Herpesvirus Bacterial Artificial Chromosome Technology For Antifertility Vaccination
                    of Foxes in Australia
                    T. Strive, J. Wright, N. French, C. M. Hardy, G. H. Reubel
                    Sustainable Ecosystems, CSIRO, Canberra ACT, AUSTRALIA.

                P73 Molecular Cloning and Sequence Analysis of Bm86 cDNA from a Thai Strain of the Cattle Tick,
                    Boophilus microplus
                    S. Jittapalapong1, S. Thanasilp1, T. Sirinarukmitr2, K. Kaewmongkol3, R. W. Stich4
                    1Veterinary Parasitology, Kasetsart University, Bangkok, THAILAND, 2Veterinary

                    Pathology, Kasetsart University, Bangkok, THAILAND, 3Veterinary Companion Animal
                    Medicine, Kasetsart University, Bangkok, THAILAND, 4Veterinary Preventive Medicine,
                    The Ohio State University, Columbus, OH.

                P74 Intranasal Vaccination of Mares to Protect Against Streptococcal Uterine Infections
                    R. C. Causey
                    Animal and Veterinary Sciences, University of Maine, Orono, ME.

                P75 CpG Oligodeoxynucleotides Upregulate Antibacterial Systems and Induce Early, Non-specific
                    Antiviral Protection in Fish.
                    A. C. Carrington1, B. Collet2, C. J. Secombes1
                    1Department of Zoology, University of Aberdeen, Aberdeen, UNITED KINGDOM,
                    2Fisheries Research Services, Marine Laboratory, Aberdeen, UNITED KINGDOM.



                P76 Summary of the Research of Recombinant HEV Vaccine
                    J. Lin
                    Lanzhou Institute of Biological Products, Gansu, CHINA




38
on Vaccine Research




     MEET THE
      EXPERT
    PRESENTERS




                      39
      Eighth Annual Conference
                                     MEET THE EXPERT PRESENTERS
W. Ripley Ballou, M.D.                                       Disease Control and Prevention (CDC). He is also the
                                                             Director of the Respiratory and Meningeal Pathogens
Meet the Experts Breakfast Session
                                                             Research Unit at the University of the Witwatersrand in
Tuesday, May 10, 2005                                        Johannesburg, South Africa.
7:00 am – 7:45 am                                                He was previously the Director of the South African
                                                             Institute for Medical Research in South Africa. He did
    Dr. Ballou is Vice President, Early Development,         his undergraduate training and specialization in South
GlaxoSmithKline Biologicals in Rixensart Belgium. He         Africa, and his post doctoral research at Rockefeller
is responsible for the clinical development of vaccines      University in New York.
against malaria, tuberculosis, HIV, as well as other early       Professor Klugman has served as a member of
development projects. Prior to his position at GSK, Dr.      numerous international committees including those
Ballou was Vice President, Vaccines and Infectious           of the World Health Organization in Geneva and the
Diseases at MedImmune, Inc. From 1984 to 1999, Dr.           Institute of Medicine in Washington, DC. He currently
Ballou was an Infectious Disease Officer with the US         chairs the Wellcome Trust Tropical Interview Panel in
Army where his research focused on the development of        London. He serves as an editor or member of the
malaria vaccines. From 1991 until his retirement from        editorial board of 9 international journals on medicine,
the military in 1999, he served as Chief, Department of      infectious diseases and antimicrobial research.
Immunology, Walter Reed Army Institute of Research               Professor Klugman’s research interests are in
and was responsible for the Army’s malaria vaccine           determinants of antimicrobial resistance, the clinical
development program.                                         relevance of resistance and the development of vaccines
    Dr. Ballou received his bachelor’s degree from the       for bacterial pathogens – particularly the pneumococcus.
Georgia Institute of Technology, Atlanta, Georgia, and       He has published more than 300 papers in the scientific
his medical degree from Emory University. He received        literature to date.
his internal medicine and infectious diseases training at
the Walter Reed Army Medical Center.
    Dr. Ballou has authored and/or coauthored more           Karen L. Kotloff, M.D.
than 135 research papers and book chapters on
infectious disease topics. In addition, as an editorial
                                                             Meet the Experts Breakfast Session
board member, he has reviewed several scientific             Tuesday, May 10, 2005
journals and numerous proceedings.                           7:00 am – 7:45 am

                                                                 Dr. Kotloff is Professor of Pediatrics and Medicine at
Keith P. Klugman, M.D., Ph.D.                                the University of Maryland School of Medicine and
Meet the Experts Breakfast Session                           Chief of the Community Studies Section of the Center
                                                             for Vaccine Development. She received her bachelor’s
Tuesday, May 10, 2005                                        degree from Washington University in St. Louis,
7:00 am – 7:45 am                                            Missouri and her medical degree from Temple University
                                                             in Philadelphia, Pennsylvania. She completed her
   Keith Klugman MB BCh, PhD, FRCPath (Lond) is              residency in Pediatrics at the Children’s Hospital of
currently Professor of Global Health at the Rollins          Pittsburgh and her fellowship in Infectious Diseases at
School of Public Health at Emory University, in              the University of Maryland.
Atlanta, GA, USA. He is also Professor of Medicine in            Dr. Kotloff has 18 years experience conducting
the Division of Infectious Diseases of the School of         epidemiologic research in infectious diseases and Phase I,
Medicine at that University and a Visiting Researcher        II, and III clinical vaccine trials involving adults and
in the Respiratory Diseases Branch of the Centers for        children. She has particular interest in vaccines against


40
on Vaccine Research
                                 MEET THE EXPERT PRESENTERS
enteric infections, including Shigella, C. difficile, and      Award of the Pan American Society for Clinical Virology.
Helicobacter pytori, among others. Recently, Dr. Kotloff       In June 1998, he received the French Legion of Honor
helped to establish a field site for evaluating vaccines and   Medal, in June 2001, the Distinguished Alumnus Award
vaccine preventable diseases in Mali, West Africa.             of the Children’s Hospital of Philadelphia, the Sabin
   Dr. Kotloff has served as a consultant for the National     Gold Medal in May 2002, and in September 2004 the
Institutes of Health, the International Vaccine Institute,     Bristol Award of the Infectious Diseases Society of
and the World Health Organization. She has authored            America. A lecture in his honor has been established at
or co-authored more than 75 research papers and book           the Pediatric Academic Societies annual meeting. His
chapter on infectious disease topics.                          bibliography includes over 600 articles and he has edited
                                                               several books including the standard textbook on
                                                               vaccines. He developed the rubella vaccine now in
                                                               standard use, and has worked extensively on the
Stanley A. Plotkin, M.D.                                       development and application of other vaccines including
Meet the Experts Breakfast Session                             polio, rabies, varicella, rotavirus and cytomegalovirus.
Tuesday, May 10, 2005
7:00 am – 7:45 am
                                                               Gregory A. Poland, M.D.
   Dr. Stanley A. Plotkin is Emeritus Professor of the         Meet the Experts Breakfast Session
University of Pennsylvania and Executive Advisor to            Tuesday, May 10, 2005
Sanofi Pasteur. Until 1991, he was Professor of Pediatrics
and Microbiology at the University of Pennsylvania, and        7:00 am – 7:45 am
Professor of Virology at the Wistar Institute and at the
same time, Director of Infectious Diseases and Senior             Dr. Gregory Poland is the Director of the Mayo
Physician at the Children’s Hospital of Philadelphia. In       Clinic's Vaccine Research Group – a state-of-the-art
1991, Dr. Plotkin left the University to join the vaccine      research group and laboratory that investigates issues
manufacturer, Pasteur-Mérieux-Connaught, where for             surrounding vaccine response and novel vaccines
seven years he was Medical and Scientific Director,            important to public health. Dr. Poland is a Professor
based at Marnes-la-Coquette, outside Paris. The same           of Medicine and Infectious Diseases and Molecular
company is now named Sanofi Pasteur.                           Pharmacology and Experimental Therapeutics, the
   Dr. Plotkin’s career included internship at Cleveland       Associate Chair for Research for the Department of
Metropolitan General Hospital, residency in pediatrics         Medicine, the Director of the Immunization Clinic
at the Children’s Hospital of Philadelphia and the             and the Director of the Program in Translational
Hospital for Sick Children in London and three years           Immunovirology and Biodefense at the Mayo Clinic.
in the Epidemic Intelligence Service of the Centers for        He also serves as the President of the International
Disease Control of the US Public Health Service.               Society for Vaccines and the American Editor for the
   He has been chairman of the Infectious Diseases             Journal Vaccine.
Committee and the AIDS Task Force of the American                 In March 2005, Dr. Poland was elected as the
Academy of Pediatrics, liaison member of the Advisory          President of the Armed Forces Epidemiological Board.
Committee on Immunization Practices and Chairman               He was appointed as the Mary Lowell Leary Professor in
of the Microbiology and Infectious Diseases Research           Medicine (the highest academic distinction for a faculty
Committee of the National Institutes of Health.                member) by Mayo Clinic’s Board of Trustees in
Dr. Plotkin received the Bruce Medal in Preventive             February 2004, and in May 2003, he was awarded the
Medicine of the American College of Physicians, the            Secretary of Defense Medal for Outstanding Public
Distinguished Physician Award of the Pediatric                 Service. In 1998, he received a joint award from the
Infectious Diseases Society and the Clinical Virology          Centers for Disease Control and Prevention and the



                                                                                                                     41
      Eighth Annual Conference
                                    MEET THE EXPERT PRESENTERS
Health Care Financing Administration for his                  antigens of unrelated pathogens and deliver them to the
contribution to increasing adult immunization rates in        human immune system. His clinical research has
the US which was awarded by the Surgeon General of            involved studies of pathogenesis and the assessment of a
the United States. Also of major significance, in 1997,       variety of vaccines in adults and children in Baltimore,
he was honored as the "Outstanding Clinical                   as well as in many developing countries. He has been
Investigator of the Year" by the Mayo Clinic.                 a pioneer in carrying out clinical trials in developing
   Additionally, Dr. Poland participates on many              countries, including studies of vaccines developed at
national and academic review committees and reviews           the CVD. He designed, arranged and supervised the
journal articles for over 26 different publications such as   performance of several large-scale, randomized,
The Lancet, Annals of Internal Medicine and New England       controlled field trials investigating the efficacy of live
Journal of Medicine. A prolific writer, Dr. Poland has        oral typhoid vaccines (which led to licensure of Ty21a
published over 160 peer-reviewed scientific articles and      by the FDA) and a vaccine to prevent invasive disease
book chapters.                                                caused by Haemophilus influenzae type b.
   Dr. Poland received his medical degree from the               Dr. Levine received his B.S. degree from City College
Southern Illinois University School of Medicine in            of New York, his Medical degree from the Medical
Springfield, Illinois, and completed his residency and        College of Virginia, and his D.T.P.H. diploma (with
advanced post-graduate work at the University of              Distinction) from the London School of Hygiene and
Minnesota/Abbott-Northwestern Hospital,                       Tropical Medicine.
Minneapolis, MN.                                                 Dr. Levine currently sits on the editorial board of
                                                              four major research journals, is a consultant to many
                                                              organizations including the World Health Organization,
                                                              NIH, Institute of Medicine and the Department of
Myron M. Levine, M.D., D.T.P.H.
                                                              Defense. He holds memberships in numerous societies
Meet the Experts Breakfast Session                            including the Institute of Medicine of the National
Wednesday, May 11, 2005                                       Academy of Science, the Association of American
7:00 am – 7:45 am                                             Physicians, the American Society of Clinical
                                                              Investigation and the Interurban Clinical Club. He is
                                                              past President of the American Epidemiological Society
   Myron M. Levine, M.D., D.T.P.H, Director of
                                                              and most recently was voted as President-elect of the
the internationally recognized Center for Vaccine
                                                              American Society of Tropical Medicine and Hygiene.
Development at the University of Maryland School of
                                                              He is the recipient of many honors, two of which are the
Medicine, holds faculty appointments as Professor in
                                                              Albert B. Sabin Gold Medal Award for lifetime
four departments at the University and is Chief of two
                                                              achievement in the area of vaccine development and
divisions. Dr. Levine has been Director of the Center
                                                              implementation and he was voted by the editors of
for Vaccine Development since its inception, and has
                                                              Baltimore Magazine as “Baltimorean of the Year.” This
created therein an environment that is unusually rich
                                                              honor was bestowed upon ten individuals in recognition
in intellectual ferment and stimulation.
                                                              of their contribution to improving the way of life in
   He is one of the most vocal advocates of mucosal           Baltimore in 2001.
immunization, i.e., the administration of vaccines by
                                                                 Dr. Levine has authored and co-authored 445
oral and intranasal routes to avoid the unpleasantness
                                                              scientific articles, 94 chapters, and is senior editor of
and occasional dangers of parenteral injections.
                                                              “New Generation Vaccines,” the third edition premier
Dr. Levine has made substantial contributions in basic
                                                              text on the discipline of modern vaccinology published
vaccinology and clinical research. In recent years, his
                                                              in January 2004.
basic laboratory research has focused on the use of
attenuated Salmonella typhi as live oral typhoid vaccines
and as live vector vaccines that express the protective


42
on Vaccine Research
                               MEET THE EXPERT PRESENTERS
Peter L. Nara, D.V.M., Ph.D.                                  Dr. Nara’s formal education and training include
                                                           his Bachelors of Science with Honors in 1977 from
Meet the Experts Breakfast Session
                                                           Colorado State University; his Masters of Science, cum
Wednesday, May 11, 2005                                    laude in Immuno-pharmacology in 1979 from The Ohio
7:00 am – 7:45 am                                          State University; his combined Doctor of Veterinary
                                                           Medicine in 1984 and Doctorate of Philosophy in
   Dr. Nara is currently Chief Executive Officer,          Retrovirology and Immunology in 1986 from The Ohio
President, Chairman & co-founder of Biological             State University. His post-doctoral training involved a
Mimetics, Inc., a biotechnology company founded            dual 4-year combined National Institutes of Health
to translate the theory of “Deceptive Imprinting” and      (NIH) medical post-doctoral fellowship/Veterinary
the “Immune Refocusing” Technology, discovered by          Medical Officer at the National Cancer Institute, and a
Dr. Nara and colleagues, into preventative vaccines,       4-year Comparative Pathology Residency at the Armed
novel immuno-therapeutics and diagnostics to               Forces Institute of Pathology, Washington D.C. (1986-
ameliorate disease worldwide. Prior to this position,      1990). He was acting Head of the Virus Biology Section
Dr. Nara was formerly the Section Chief of the Vaccine     in the Office of the Institute’s Director from 1990-1992
Resistant Diseases Section, Division of Basic Sciences,    and was tenured and promoted to and remained Section
at the National Cancer Institute, National Institutes of   Chief of the Virus Resistant Diseases Section from
Health.                                                    1993-1998.
   Dr Nara’s scientific contributions include over 20
book chapters and 160 scientifically peer-reviewed
publications. Some highlights include: his laboratory      George R. Siber, M.D.
at the National Cancer Institute was designated both a     Meet the Experts Breakfast Session
National and International AIDS Reference Laboratory
by the National Institute’s of Allergy and Infectious      Wednesday, May 11, 2005
Diseases and World Health Organization (WHO),              7:00 am – 7:45 am
Global Program on AIDS; he initiated a International
effort which characterized over 120 HIV-1 isolates for        Dr. Siber joined Wyeth Lederle Vaccines as Vice
future vaccine and clinical trial site development from    President and Chief Scientific Officer in August 1996.
epidemic centers around the world, was made the HIV-1      He was named Senior Vice President in August 1999
Immunotyping Group leader and chairman for the             and Executive Vice President in June 2002. In this
WHO Network for HIV Isolation and Characterization.        capacity Dr. Siber is responsible for discovery research
He serves on numerous scientific advisory boards of        in bacterial vaccines, viral vaccines, immunology and
corporate, private foundations and academic initiatives    genetic vaccines, process and analytical development,
in the area of national biodefense, comparative medicine   clinical development, and scientific affairs for Wyeth
and immunology, vaccine discovery and immuno-              Vaccines Research. While at Wyeth Dr. Siber has
therapeutics. He was a Howard Hughes, Ciba Corning,        overseen the development and approval of an acellular
and Miles Invited Lecturer, nominated by Dr. Jonas         pertussis vaccine for infants (Acel-Imune), a vaccine to
Salk; elected, and served as Founding President of the     prevent Rotavirus diarrhea in infants (RotaShield),
International Society for Vaccines 1994-2002; is one of    a glycoconjugate vaccine to prevent group C
the founding co-chairs for the Annual Conference on        meningococcal meningitis (Meningitec), a 7 component
Vaccine Research; served on the editorial boards of the    glycoconjugate vaccine to prevent pneumococcal disease
leading virology, AIDS, vaccine, immunology journals;      in infants and children (Prevnar), and a cold adapted
and is the inventor or co-inventor on 7 issued U.S.        nasally administered influenza vaccine in collaboration
patents. This past year he was nominated as                with MedImmune (FluMist).
Biotechnology Executive of the Year in Frederick,             Prior to joining Wyeth Dr. Siber was Director of
County, Maryland.                                          the Massachusetts Public Health Biologic Laboratories


                                                                                                                 43
      Eighth Annual Conference
                                   MEET THE EXPERT PRESENTERS
and Associate Professor of Medicine with the Harvard        Connie Schmaljohn, Ph.D.
Medical School, Dana Farber Cancer Institute.
                                                            Meet the Experts Breakfast Session
During this time Dr. Siber oversaw research on acellular
pertussis and Hemophilus influenza vaccines, the            Wednesday, May 11, 2005
development and approval of CMV Immune Globulin             7:00 am – 7:45 am
(Cytogam®) and RSV Immune Globulin (Respigam®)
and the production of DTP vaccines and immune                  Dr. Connie Schmaljohn is Chief of the Molecular
globulins for the State of Massachusetts.                   Virology Department at the United States Army Medical
   Dr. Siber’s research interests have included the         research Institute of Infectious Diseases (USAMRIID).
evaluation of the human immune response to                  She received her bachelors degree in Microbiology from
polysaccharide and protein antigens, the development        the University of Nebraska and her Ph.D. in
of vaccines and immune globulins against Hib,               Microbiology/Virology from Colorado State University.
pneumococci, meningococci, pertussis and RSV and               Dr. Schmaljohn made key contributions to the
maternal immunization to prevent perinatal and early        discovery and characterization of hantaviruses and
neonatal infections. Dr. Siber has authored more than       remains a leading expert in hantavirus research. Most
150 scientific articles in peer-reviewed journals. Dr.      recently, her research has focused on molecular vaccine
Siber holds 3 issued patents which support a licensed       development with an emphasis on multiagent DNA
diagnostic test for meningitis (Bactigen®) and an           vaccines for hantaviruses, bunyaviruses, flaviviruses,
antibody based preventative for respiratory syncytial       alphaviruses, and filoviruses.
virus infections in high-risk children (Respigam®).            Dr. Schmaljohn holds committee positions in the
   Dr. Siber has served on numerous advisory                American Society for Virology and the American Society
committees including the WHO/UNDP Steering                  for Tropical Medicine and Hygiene and is an Editorial
Committee for Encapsulated Bacterial Vaccines, the          Board member for Virology, Emerging Infectious Diseases,
Steering Committee for Development of Streptococcus         Journal of Virology, Virology Journal, and Virus Research.
Pneumonia Vaccine for the Pan American Health                  Dr. Schmaljohn has coauthored more than 110
Organization, the Institute of Medicine Committee           research papers, reviews and book chapters and has
on the Children’s Vaccine Initiative, the NIH Blue          edited several books.
Ribbon Panel for Bioterrorism and its Implications for
Biomedical Research, Chairman of the review of the
US Army’s HIV research program, and the Board of
Scientific Counselors for the National Vaccine Center.
   Dr. Siber was the recipient of the Canadian Medical
Research Council Fellowship and is currently a fellow
of the Infectious Diseases Society of America and the
Pediatric Infectious Disease Society. Dr. Siber received
a B.Sc. degree at Bishop’s University and a MDCM
degree from McGill University both in Quebec, Canada.
Dr. Siber trained as a medical intern and resident at
Rush Presbyterian Medical Center in Chicago and as a
senior resident and infectious disease specialist at Beth
Israel Hospital and Children’s Hospital in Boston.




44
on Vaccine Research




   ABSTRACTS OF
      INVITED
  PRESENTATIONS




                      45
         Eighth Annual Conference
                                       ABSTRACTS OF INVITED PRESENTATIONS
          Dilemmas in Public Health: From Smallpox to Polio, SARS and                    Use of Conjugate Vaccines as a Probe to Define the Role of the
1         Avian Influenza
          D. Heymann
                                                                               2         Pneumococcus in the Etiology of Pneumonia
                                                                                         K. Klugman
          World Health Organization, Geneva, Switzerland                                 Emory University, Department of International Health, Atlanta, GA

     Smallpox vaccine, effectively used in a worldwide eradication                 The bacterial etiology of pneumonia is underestimated as
programme, led to certification of smallpox eradication in 1980. In            diagnostic tests such as blood culture have very poor sensitivity.
1981, less than a year afterwards, AIDS was first identified. It is now        Conjugate vaccine trials have documented that the bacterial pathogens
understood that had smallpox not been eradicated before AIDS                   Haemophilus influenzae and Streptococcus pneumoniae each cause 20 -
transmission began to amplify worldwide, it would have been difficult          37% of bacterial pneumonia in children with X-ray documentation.
if not impossible to eradicate using the same vaccine. The smallpox            These remain underestimates given the impact of misclassification on
eradication saga continues today as the threat of deliberate use of the        this method of assessment. Non specific inflammatory markers such as
smallpox virus to cause harm, perceived by some nations, has led to an         procalcitonin and C reactive protein may increase the specificity of the
active smallpox research programme for new vaccines and antivirals,            X-ray diagnosis of bacterial pneumonia. These bacteria may also play a
using infective smallpox virus that was not destroyed after eradication.       significant role in hospitalization of patients infected with respiratory
Efforts towards the eradication of a second viral disease, polio, have         viruses. It is probable that the mortality associated with the 1918
recently been intensified and it is now feasible that polio transmission       influenza pandemic was associated with a pneumococcal epidemic
could be interrupted by the end of 2005. It is a paradox that the              among young adults in overcrowded conditions. Conjugate vaccine
vaccine being used for polio eradication worldwide - trivalent oral            administered to infants has been shown to reduce the burden of
polio vaccine (OPV) - will itself become a risk after polio has been           invasive pneumococcal disease in adults. The role that conjugate
eradicated because of recombination events that produce vaccine-               vaccine administration to children or adults may play in the
derived polioviruses (VDPV). VDPV will change the risk benefit of              prevention of pneumonia in the elderly remains to be established in
OPV once wild poliovirus has been eradicated, requiring that its use be        clinical trials. Conjugate pneumococcal vaccine may play a role in
discontinued. SARS, for which there was no vaccine, is thought to              reducing mortality from pneumonia in both children and adults.
have emerged into human populations in China sometime in late
2002. As many other emerging infections, SARS spread                           References:
internationally, infected a disproportionate number of health workers,         1. Klugman KP et al. A trial of a 9-valent pneumococcal conjugate
required a worldwide effort to contain, and caused severe economic                vaccine in children with and those without HIV infection. N Engl J
loss. Vaccine development, begun with enthusiasm by several                       Med. 2003; 349:1341-8.
pharmaceutical companies, some with government funding, has now                2. Black SB et al. Effectiveness of heptavalent pneumococcal conjugate
decreased as further understanding about SARS epidemiology has                    vaccine in children younger than five years of age for prevention of
become clear. And finally, the challenge of avian influenza has shown             pneumonia. Pediatr Infect Dis J 2002; 21:810-5.
the importance of increasing vaccine production capacity in a world            3. Madhi SA, Klugman KP, Vaccine Trialist Group. A role for
where annual influenza vaccine production is less than 300 million                Streptococcus pneumoniae in virus-associated pneumonia. Nat Med.
doses, and the need to scale up production of a new influenza vaccine             2004;10:811-3.
is a continuing, but poorly understood possibility.                            4. Cutts FT et al. Efficacy of nine-valent pneumococcal conjugate
                                                                                  vaccine against pneumonia and invasive pneumococcal disease in
References:                                                                       The Gambia: randomised, double-blind, placebo-controlled trial.
1. Heymann DL, Aylward RB. Perspective article. Global Health:                    Lancet 2005;365:1139-46.
   Eradicating Polio. New England Journal of Medicine, 2004, 351 (13):
   1275-1277.
2. Heymann DL, de Gourville EM, Aylward RB. Protecting investments
   in polio eradication: the past, present and future of surveillance for                Avidity and Biological Activity of Antibodies Elicited by
   acute flaccid paralysis. Epidemiology and Infection, October 2004, 132
   (5): 779-80.
                                                                               3         Pneumococcal, Hib, and Meningococcal Conjugate Vaccines
                                                                                         D. Goldblatt
3. Heymann DL. Smallpox containment updated: considerations for the                      University College of London, London, UK
   21st century. International Journal of Infectious Diseases, October 2004,
   8 (S2): S15-S20 (ISSN 1201-9712).                                               Conjugate vaccines for Streptococcus pneumoniae, Haemophilus
4. Heymann DL, Rodier G. SARS: Lessons from a new disease. Knobler             influenzae type b and Neisseria meningitidis Group C have changed the
   S, Mahmoud A, Lemon S, Mack A, Sivitz L, Oberholtzer K, eds.                face of pediatric infectious diseases. These three pathogens have in
   Learning from SARS. Preparing for the Next Disease Outbreak. Workshop       common a capsular polysaccharide (of different chemical structure),
   Summary. Washington, DC, USA, The National Academies Press,                 which gives them a unique advantage. Their capsules prevent the
   2004: 234-246.                                                              deposition of complement and are thus important virulence factors
                                                                               allowing them to evade host immunity yet conversely are targets for
                                                                               protective antibody. Young children are unable to efficiently mount an
                                                                               immune response (of which the most important is antibody) to
                                                                               polysaccharide antigens, explaining their susceptibility to invasive
                                                                               disease with these organisms. Conjugation of capsular polysaccharide
                                                                               to a protein carrier has resulted in glycoconjugate vaccines that induce
                                                                               protective antibodies to polysaccharide when administered in the first
                                                                               few months of life. The protein carrier has the effect of changing the


46
  on Vaccine Research
                                    ABSTRACTS OF INVITED PRESENTATIONS
                                                                          5
immune response to the capsular polysaccharides by recruiting T cells               Results of the Pneumococcal Conjugate Vaccine Trial
to help polysaccharide specific B cells make antibodies. In addition to             F. Cutts
their enhanced immunogenicity, and in contrast to polysaccharide                    World Health Organization, Geneva, Switzerland
vaccines, conjugate vaccines induce immunological memory. One
measurable marker of that memory, is avidity maturation, an increase          Pneumonia is estimated to cause 2 million deaths each year in
in the strength with which antibody binds to antigen, demonstrable in     children. Streptococcus pneumoniae is the most important cause of severe
the months following priming. Avidity is also an important                pneumonia. We conducted a randomised, placebo-controlled double-
component of the function of antibody, with animal models                 blind trial in rural Gambia of a nine-valent pneumococcal conjugate
suggesting protection can be achieved with less high compared to low      vaccine, with the primary objective of evaluating efficacy against a first
avidity antibody. Such direct relationship in the protection of humans    episode of radiological pneumonia. We randomised children aged 6-51
has proven more difficult to illustrate.                                  weeks to receive 3 doses of pneumococcal conjugate vaccine or placebo
                                                                          with intervals of at least 4 weeks between doses. We conducted
Reference:                                                                surveillance for radiological pneumonia, invasive disease and adverse
1. Jodar L, Butler J, Carlone G, Dagan R, Goldblatt D, Kayhty H,          events at a major health centre and hospital. We monitored mortality by
   Klugman K, Plikaytis B, Siber G, Kohberger R, Chang I, Cherian         recording outcome of admissions and conducting three-monthly home
   T. Serological criteria for evaluation and licensure of new            visits to each child. In per-protocol analyses, pneumococcal vaccine
   pneumococcal conjugate vaccine formulations for use in infants.        efficacy was 37% (95% CI: 27, 45) against radiological pneumonia;
   Vaccine. 2003 Jul 4;21(23):3265-72.                                    77% (95% CI: 51, 90) against vaccine-type invasive pneumococcal
                                                                          disease; 50% (95% CI: 21, 69) against all invasive pneumococcal
                                                                          disease; 15% (95% CI: 7, 21) against all-cause admissions, and 16%
                                                                          (95% CI: 3, 28) against mortality. In this rural African setting,
          Long-term Immunologic Memory: Insights from the UK              pneumococcal conjugate vaccine has high efficacy against pneumonia
4         Experience with Haemophilus Influenzae Type b and
          Meningococcal C Conjugates
                                                                          and invasive pneumococcal disease, and can significantly reduce hospital
                                                                          admissions and improve child survival.
          E. Miller
          Communicable Disease Surveillance Center, London, UK            Reference:
                                                                          1. Cutts FT, Zaman SM, Enwere G, Jaffar S, Levine OS, Okoko JB, et.
    In the UK Hib was introduced as a primary immunization in                al.; Gambian Pneumococcal Vaccine Trial Group. Efficacy of nine-
1992 at 2/3/4 months of age (the schedule used for DTP vaccine)              valent pneumococcal conjugate vaccine against pneumonia and
without a booster because it was thought that immunologic memory             invasive pneumococcal disease in The Gambia: randomised, double-
induced in infancy would provide long-term protection. The same              blind, placebo-controlled trial. Lancet 2005;365:1139-46.
logic was applied to meningococcal serogroup C conjugate (MCC)
vaccine introduced in 1999 in the UK, the first country to license this
new vaccine based purely on immunologic correlates of protection
without supporting efficacy data. Clinical trials with MCC vaccine                  New Conjugate Vaccine to Prevent Anthrax
had confirmed that it induced immune memory which persisted for at
least 3 years after primary immunization in infants. The subsequent
                                                                          6         J. Robbins
                                                                                    National Institute of Child Health and Human Development, NIH,
resurgence of Hib disease in the UK in 1999 and the rapid decline in                Bethesda, MD
efficacy with MCC vaccines within one year after completion of
infant immunization has prompted a major rethink of the role of               Both the protective antigen (PA) and the poly(gamma-d-glutamic
immune memory in long term protection. Interestingly, efficacy of         acid) capsule (gamma dPGA) are essential for the virulence of Bacillus
both Hib and MCC vaccines, and antibody levels, persist better in         anthracis. A critical level of vaccine-induced IgG anti-PA confers
older age groups (>1 year) given a single dose but no subsequent          immunity to anthrax, but there is little or no information about the
boosters. Despite the decline in efficacy of MCC vaccine in the           protective action of IgG anti-gamma dPGA. Because the number of
younger age groups, the control of the disease in the UK is still         spores resulting from exposure due to a bioterrorist event might be
excellent. It is now clear, informed by mathematical models of carriage   greater than encountered in nature, we sought to induce capsular
and disease, that protection against carriage induced by the conjugate    antibodies to expand the immunity conferred by available anthrax
vaccines has made a major contribution to the success of the Hib and      vaccines. Non-immunogenic gamma dPGA or corresponding synthetic
MCC vaccine programs. The immunologic correlates of long-term             peptides were bound to bovine serum albumen, recombinant B.
protection with conjugate vaccines remain unclear.                        anthracis PA (rPA), or recombinant Pseudomonas aeruginosa exotoxin A
                                                                          (rEPA). To identify the optimal construct, conjugates of B. anthracis
Reference:                                                                gamma dPGA, Bacillus pumilus gamma dLPGA, and peptides of varying
1. Snape MD, Pollard AJ. Meningococcal polysaccharide-protein             lengths (5-, 10-, or 20-mers), of the d or l configuration with active
   conjugate vaccines. Lancet Infect Dis. 2005 Jan;5(1):21-30             groups at the N or C termini, were bound at 5-32 mol per protein. The
                                                                          conjugates were characterized by physico-chemical and immunological
                                                                          assays, including GLC-MS and matrix-assisted laser desorption
                                                                          ionization time-of-flight spectrometry, and immunogenicity in 5- to 6-
                                                                          week-old mice. IgG anti-gamma dPGA and antiprotein were measured
                                                                          by ELISA. The highest levels of IgG anti-gamma dPGA were elicited by
                                                                          decamers of gamma dPGA at 10 -20 mol per protein bound to the N- or
                                                                                                                                          (continued)


                                                                                                                                                     47
         Eighth Annual Conference
                                         ABSTRACTS OF INVITED PRESENTATIONS
C-terminal end. High IgG anti-gamma dPGA levels were elicited by             of populations, including persons in healthcare facilities, in the military
two injections of 2.5 microg of gamma dPGA per mouse, whereas                and on cruise ships. The impact of these viruses as causes of foodborne
three injections were needed to achieve high levels of protein               and waterborne disease indicates that development of an effective
antibodies. rPA was the most effective carrier. Anti-gamma dPGA              vaccine would be useful. However, there are many challenges that must
induced opsonophagocytic killing of B. anthracis tox-, cap+. gamma           be overcome. Human noroviruses cannot be grown in cell culture and
dPGA conjugates may enhance the protection conferred by PA alone.            no small animal model of infection exists. However, a human challenge
gamma dPGA-rPA conjugates induced both anti-PA and anti-gamma                model is available. The antigenic and genetic diversity of noroviruses
dPGA.                                                                        will likely complicate the development of a broadly effective vaccine.
                                                                             Furthermore, correlates of immunity to noroviruses are poorly defined,
References:                                                                  although recent studies have shown that lack of expression of certain
1. Schneerson R, Kubler-Kielb J, Liu TY, Dai ZD, Leppla SH, Yergey           histo-blood group antigens is associated with resistance to infection by
   A, Backlund P, Shiloach J, Majadly F, Robbins JB. Poly(gamma-D-           Norwalk virus. Expression of the structural proteins of Norwalk virus
   glutamic acid) protein conjugates induce IgG antibodies in mice to        leads to the formation of virus-like particles (VLPs) that are
   the capsule of Bacillus anthracis: a potential addition to the anthrax    immunogenic when administered to mice and humans. Norwalk virus
   vaccine. Proc Natl Acad Sci U S A. 2003; 100:8945-50.                     VLPs are currently under investigation as a potential vaccine candidate.
2. Leppla SH, Robbins JB, Schneerson R, Shiloach J. Development of
   an improved vaccine for anthrax. J Clin Invest. 2002; 110:141-4.          References:
                                                                             1. Estes MK, Ball JM, Guerrero RA, Opekun AR, Gilger MA, Pacheco
                                                                                SS, Graham DY. Norwalk virus vaccines: challenges and progress.
                                                                                J Infect Dis 2000;181:S367-73.
          New Rotavirus Vaccines
7
                                                                             2. Tacket CO, Mason HS, Losonsky G, Estes MK, Levine MM, Arntzen
          D. Steele                                                             CJ. Human immune responses to a novel Norwalk virus vaccine
          World Health Organization, Geneva, Switzerland                        delivered in transgenic potatoes. J Infect Dis 2000;182:302-5.
                                                                             3. Hutson AM, Atmar RL, Estes MK. Norovirus disease: changing
    Rotavirus remains the most common cause of severe acute                     epidemiology and host susceptibility factors. Trends Microbiol
gastroenteritis in infants and young children worldwide and is                  2004;12:279-87.
associated with approximately half a million childhood deaths each
year.
    Rotavirus vaccine development progresses rapidly with major
involvement from the international pharmaceutical industry and the                    Immunology and Potential Vaccine Prevention of
creation of the GAVI-funded Rotavirus Vaccine Program. Recently,
alternative vaccine candidates have been taken up by vaccine producers
                                                                             9        Clostridium difficile Colitis
                                                                                      K. Kotloff
in developing countries. Although certain rotavirus vaccines have been                University of Maryland School of Medicine, Baltimore, MD
licensed in local national settings, and some candidates have
completed enormous safety and efficacy trials, none of the various               Clostridium difficile is a major cause of nosocomial diarrhea,
candidates have shown their clinical efficacy in infants in the              particularly affecting the elderly and immunocompromised. Although
developing countries of Africa and Asia.                                     usually responsive to medical therapy, infection can increase morbidity,
    Challenges to rotavirus vaccine development include the lack of          prolong hospitalization, and produce life-threatening colitis. Toxins
efficacy data in infant populations most at risk of the disease;             A and B are the principal virulence factors of this noninvasive organism.
interaction with other routine EPI vaccines, especially OPV; safety          Considerable evidence supports the role of antitoxic immunity, most
issues such as the risk of intussusception and administration to HIV-        notably against toxin A, in prevention of and recovery from C. difficile-
infected infants. Finally, issues such as supply and price of the vaccines   associated diarrhea (CDAD). Vaccines that induce antitoxic immunity
and equity of distribution of these new vaccines to the regions where        are thus being explored as a means for protecting high-risk individuals.
they are most needed have not been creatively addressed yet by the           Approaches showing promise in preclinical models include recombinant
international community nor the countries.                                   fusion proteins containing the nontoxic binding domain of toxin A and
                                                                             delivered to the mucosa either directly (with adjuvant) or via a live
Reference:                                                                   attenuated bacterial vector. In the clinical arena, a Phase 1 trial has been
1. Glass R, Bresee J, Parashar U, Jiang B, Gentsch J. The future of          completed to evaluate a parenteral vaccine containing C. difficile toxoids
   rotavirus vaccines: a major setback leads to new opportunities. The       A and B. Thirty healthy adults received four spaced inoculations on
   Lancet 363:1547-1550, May 2004                                            days 1, 8, 30 and 60 with either 6.25 Fg, 25 Fg, or 100 Fg of vaccine.
                                                                             Vaccination was generally well-tolerated. Nearly all subjects ($90%)
                                                                             developed vigorous serum antibody responses to both toxins, as
                                                                             measured by IgG ELISA and neutralization of cytotoxicity, whereas fecal
          Progress in Vaccines Against Norwalk Virus
8
                                                                             IgA increases occurred in approximately 50%. Serum antitoxin A IgG
          R. Atmar                                                           ELISA titers in all vaccine recipients exceeded the concentrations that
          Baylor College of Medicine, Houston, TX                            have been associated with protection in clinical studies. More recently,
                                                                             the vaccine was evaluated in three patients with multiple episodes of
    Norwalk virus is a human calicivirus and is the prototype norovirus      CDAD. Strong immune responses were seen in two patients, and none
strain. Noroviruses are the most common cause of epidemic                    had additional recurrences of CDAD. Further development of this
nonbacterial gastroenteritis and are also common causes of sporadic          vaccine as a prophylactic or therapeutic agent or for producing C.
gastroenteritis. These viruses cause significant morbidity in a variety      difficile hyperimmune globulin is warranted.


48
   on Vaccine Research
                                      ABSTRACTS OF INVITED PRESENTATIONS
Reference:                                                                    century (1918, 1957, 1968). In 1997 and again in 2003-2005, a highly
1. Kotloff KL, Wasserman SS, Losonsky GA et al. Safety and                    pathogenic avian influenza virus (H5N1) has caused several cases in South-
   immunogenicity of increasing doses of a Clostridium difficile toxoid       East Asia with a mortality rate of about 70%. The most powerful means
   vaccine administered to healthy adults. Infect Immun 2001;                 to prevent and control the risk of influenza pandemics depends on the
   69(2):988-995.                                                             production and availability of vaccines. Clinical data have shown that,
                                                                              since this vaccine will be used in immunologically naive individuals, more
                                                                              than one dose may be required for optimal protection. Furthermore, due
                                                                              to the current limited vaccine manufacturing capacity globally, a dose

10        Update on Microbiology, Immunology and Vaccine Prevention
          of Dental Caries
          S. Michalek
                                                                              saving approach may be required to allow the production of sufficient doses
                                                                              of vaccine to cover the largest portion of the population worldwide. There
                                                                              is already evidence that vaccines against influenza pandemics may well
          University of Alabama at Birmingham, Birmingham, AL                 require adjuvants to be effective. Studies using the MF59 adjuvant have
                                                                              demonstrated that this target is achievable and that even immunization
    Dental caries (i.e., tooth decay) is an infectious disease that affects   with a vaccine not fully matched with the target virus can induce
the population worldwide. In the U.S., almost 80% of youth by age 17          substantial cross-reacting protective immune responses. The preparation
have experienced carious lesions. This worldwide disease is most              of vaccines effective against influenza pandemics is technically feasible.
devastating to less developed countries (see: http://www.who.int/             However, for regulatory, economical, ethical, legal and logistical reasons,
oral_health/publications/report03/en/). In the U.S. alone, dental             amongst others, this target can be only achieved through a partnership
service expenditures approximate $50 billion annually.                        between public and private sectors.
    The mutans streptococci (MS) are the primary cause of dental caries
in humans. These gram-positive bacteria selectively and specifically          Reference:
colonize tooth surfaces. An initial “window of infectivity” for MS            1. Stephenson I, Bugarini R, Nicholson K, Podda A, Wood J, Zambon M,
occurs in children around 18-24 months of age, a time corresponding              Katz J. Cross-Reactivity to Highly Pathogenic Avian Influenza H5N1
with the emergence of the primary molar teeth. Other “windows” may               Viruses after Vaccination with Nonadjuvanted and MF59-Adjuvanted
open at other stages in life. Scientific evidence from both animal and           Influenza A/Duck/Singapore/97 (H5N3) Vaccine: A Potential Priming
adult human clinical trial studies provides evidence for the effectiveness       Strategy. JID 191:1210-1215, April 2005.
and safety of active and passive immunization strategies, as well as
replacement therapy for use in obtaining protection against dental
caries. However, the effectiveness of these approaches in children,
including infants, is still needed to establish the potential use of these
approaches in this target population.
                                                                              12        Vaccines Against SARS: Where Do We Stand?
                                                                                        A. Osterhaus
                                                                                        Erasmus Medical College
                                                                                        Rotterdam, Netherlands
References:
1. Caufield PW, Cutter GR, Dasanayake AP. Initial acquisition of                  After the identification of SARS-CoV as the aetiologic agent of SARS
   mutans streptococci by infants; evidence for a discrete window of          and the rapid development of macaque-, ferret- and rodent models,
   infectivity. J. Dent. Res. 1993;72:37-45.                                  studies concerning the pathogenesis and the development of intervention
2. Childers NK, Zhang SS, Michalek SM. Oral immunization of                   strategies were vigorously pursued. Pegylated interferon-_ proved to be
   humans with dehydrated liposomes containing Streptococcus mutans           the first clinically available drug that was effective in preventing and post-
   glucosyltransferase induces salivary immunoglobulin A2 antibody            exposure treatment of SARS in the macaque model. Subsequently
   responses. Oral Microbiol. Immunol. 1994;9:146-153.                        passive transfer of neutralizing polyclonal and monoclonal antibodies was
3. Childers NK, Zhang SS, Michalek SM. Oral immunization of                   shown to significantly reduce the SARS-CoV load in the respective
   humans with dehydrated liposomes containing Streptococcus mutans           animal models, when administered preventively. Several research groups
   glucosyltransferase induces salivary immunoglobulin A2 antibody            started the development of candidate SARS vaccines, using different
   responses. Oral Microbiol Immunol. Jun 1994;9(3):146-153.                  classical and state-of-the-art technologies. It was realised that besides
4. Childers NK, Tong G, Michalek SM. Nasal immunization of                    efficacy, safety of the candidate vaccines should be given special
   humans with dehydrated liposomes containing Streptococcus mutans           attention, since it has been shown that vaccination of cats with candidate
   antigen. Oral Microbiol. Immunol. 1997;12:329-335.                         feline coronavirus vaccines predisposed them for antibody mediated
5. Childers NK, Tong G, Mitchell S, Kirk K, Russell MW, Michalek              enhanced susceptibility upon challenge. In addition, adjuvanted
   SM. A controlled clinical study of the effect of nasal immunization        inactivated whole virus vaccines should be given special attention in this
   with a Streptococcus mutans antigen alone or incorporated into             respect, since the use of candidate measles- and RSV vaccines of this type
   liposomes on induction of immune responses. Infect. Immun.                 have predisposed children for more serious disease upon infection in the
   1999;67:618-623.                                                           past. Since macaque models have been developed to study this
                                                                              phenomenon with these two candidate vaccines, it was decided to
                                                                              specifically demonstrate the absence of this phenomenon with inactivated
                                                                              candidate SARS vaccines in macaques. Besides inactivated whole virus

11        Perspective of Vaccine Manufacturers
          G. Del Giudice
          Chiron Vaccines, Siena, Italy
                                                                              vaccines, recombinant-, (MVA-; adeno-), vectored and plasmid DNA
                                                                              vaccines have now been studied in animal models for SARS. In general,
                                                                              these are aiming at the induction of a specific immune response against
                                                                              the S protein of the virus. Most of the candidate vaccines studied so far
    A generation of human-avian influenza virus reassortants has been         proved to be protective in the animal models used, with S protein specific
responsible for the three pandemic waves that hit mankind during the XX                                                                         (continued)


                                                                                                                                                        49
         Eighth Annual Conference
                                       ABSTRACTS OF INVITED PRESENTATIONS
virus neutralizing antibodies as the most likely correlate of protection.      seroprevalence of antibodies to other flaviviruses. There is considerable
No antibody-mediated enhancement has been observed, but there are              debate on what WNV will do in the future.
indications that some of the vaccines tested may predispose for the
development of immune pathology upon challenge. The first phase I              Reference:
clinical study has now been carried out in the Peoples Republic of             1. Granwehr BP, Lillibridge KM, Higgs S, Mason PW, Aronson JF,
China.                                                                            Campbell GA, Barrett ADT. West Nile virus: where are we now?
    Collectively, the data show that the collaborative activities by several      Lancet Infect Dis. 2004; 4:547-56.
research groups have not only resulted in the rapid control of the SARS
outbreak, but also to the development of preventive and therapeutic
strategies and will soon lead to the availability of effective and safe
                                                                                         Vaccination for Emergency and Emerging Animal Health Events
vaccines against SARS.
                                                                               15        R. Hill
                                                                                         United States Department of Agriculture, Washington, DC


13       Vaccines for Prevention, Management, and Eradication of Avian
         Influenza
         D. Swayne
                                                                                   The Virus-Serum-Toxin Act of 1913 provides the legal basis for the
                                                                               regulation of veterinary biologicals in the United States, and the USDA’s
                                                                               Center for Veterinary Biologics (CVB) has the authority for the issuance
         United States Department of Agriculture, Athens, GA                   of licenses and permits for such products. The law was intended to
                                                                               establish standards and control the importation of products into the
    Vaccines been used to prevent, manage and eradicate avian                  U.S. and the distribution of products assuring the purity, safety,
influenza (AI) in poultry. In the current epizootic of H5N1 AI in Asia,        potency, and efficacy of veterinary biological products. Prelicensing
vaccines have emerged to be a valuable tool in control strategies. Four        data evaluation procedures are designed to assess the quality of each
inactivated AI vaccines, based on low and high pathogenicity H5                product and support product label claims. Data from all phases of
outbreak strains, have been used in a variety of poultry including             product development are evaluated against these key elements. Under
chickens, ducks, geese and Japanese quail. Live fowl poxvirus                  the standard licensing process, this spectrum of evaluation includes
recombinants with H5 AI gene inserts will see some usage in chickens           complete characterization of seed material and ingredients, laboratory
in the near future. In addition, AI vaccine strains generated through          and host animal safety and efficacy studies. This comprehensive
reverse genetics will be used in future inactivated vaccines. Influenza        evaluation may not be possible during the emergence of a new animal
vaccines in poultry have provided intense, longer-term and broader             disease; however, there are mechanisms that allow for the availability of
protection than have influenza vaccines in humans, thus requiring less         products in an emergency animal health situation. These mechanisms
frequent change in vaccine strains than for humans. However, vaccine           include a variety of licensing/permitting options, including the
efficacy should be re-evaluated every 2-3 years against prevailing             establishment of vaccine banks. Historical examples of emerging animal
circulating AI strains. The AI vaccines provide protection by prevention       disease events in the United States will be used to illustrate the
of clinical signs and death, and reduce respiratory and intestinal virus       regulatory considerations for each type of product authorization.
replication in poultry. Differentiation of vaccinated from infected
poultry is critical to measure success of control programs.                    Reference:
                                                                               1. R.E. Hill, Jr., P.L. Foley, M.Y. Carr, L.A. Elsken, D.M. Gatewood,
Reference:                                                                        L.R. Ludemann, L.A. Wilbur. 2003. Regulatory Consideration for
1. Swayne, D.E. Application of New Vaccine Technologies for the Control           Emergency Use of Non-USDA Licensed Vaccines in the United
   of Transboundary Diseases. Develop. Biol. 119:219-228, 2004.                   States. Developments in Biologics. 114:31-52.




14       West Nile: An Overview of the Epidemic in North America
         A. Barrett
         University of Texas Medical Branch, Galveston, TX
                                                                               16       Ideas from the National Vaccine Advisory Committee,
                                                                                        the Institute of Medicine, and Academia
                                                                                        J. Klein
                                                                                        Boston Medical Center, Boston, MA
    West Nile virus (WNV) has first isolated in Uganda in 1937 and,
until recently, was found in parts of Asia, Africa and Europe. In 1999,            Recent shortages of vaccines have underlined the vulnerability of
WNV emerged in North America with an outbreak in New York and                  vaccine supply in the United States. Five key issues needed to be
surrounding areas. The virus has subsequently spread throughout the            addressed to provide a reliable and predictable supply of routinely
United States and into Canada, Mexico, Central America and Caribbean           administered vaccines: 1. Financial incentives need to be identified that
Islands. The number of human and veterinary cases has increased since          will maintain current manufacturers and encourage new manufacturers
1999, including the largest epidemic of arboviral encephalitis ever            to enter the market; 2. Regulatory constraints on development and
recorded in the Americas in 2002. In addition to “traditional” mosquito-       production of vaccines need to be reconsidered; 3. The Vaccine injury
borne transmission, the virus has been transmitted by a variety of other       Compensation Program needs to be strengthened to limit product
routes including blood-borne. The virus has been found to infect at least      liability for approved vaccines; 4. Impediments to utilization of vaccine
48 species of mosquitoes, 285 species of birds and 29 animal species.          stockpiles by Security and Exchange Commission regulations need to be
West Nile virus is clearly a major public health and veterinary problem        removed; and 5. Consumers and legislators, who now undervalue
in the United States. Surprisingly, there is little evidence of human or       vaccines and are attentive only when vaccine is unavailable, need to be
veterinary disease in Mexico, which may in part be due to the                  better informed about the assets and liabilities of vaccines. Although a


50
   on Vaccine Research
                                     ABSTRACTS OF INVITED PRESENTATIONS
variety of groups including the National Vaccine Advisory Committee,             Continuing Challenges, September 2002
the General Accounting Office, the Institute of Medicine and the Sabin        6. Sanofi pasteur: Strengthening Vaccine Supply: Principles to Ensure
Vaccine Institute have made recommendations to strengthen vaccine                Vaccine Supply, February 2002-present
supply I recent years, progress in addressing the issues of vaccine supply
has been modest. A robust domestic vaccine manufacturing capability
should be considered a national priority. Task forces, including all
vaccine constituencies (consumers, purchasers, providers, manufacturers,
regulatory authorities, national and local public health authorities,         18        A Consensus Agenda to Strengthen U.S. Vaccine Supply
                                                                                        J. Clymer
                                                                                        Partnership for Prevention, Washington, DC
scientists, advocacy groups and legislators) should be established to meet
at regular intervals until concrete proposals to strengthen vaccine supply
are developed that can be presented to authoritative agencies.                    Large gaps between U.S. adult immunization goals and actual
                                                                              vaccination rates have persisted for years, even as the gaps in pediatric
Reference:                                                                    immunization have been narrowed or eliminated. Immunization
1. National Vaccine Advisory Committee. Strengthening the Supply of           stakeholders – federal, state and local public health agencies;
   routinely Recommended Vaccines in the United States;                       manufacturers; clinical practitioners; legislators, scholars; health plans,
   Recommendations form the National Vaccine Advisory Committee.              employers; public sector purchasers; and the public – have discussed the
   JAMA 2003; 290: 3122-3128.                                                 problem and offered potential solutions but, lacking consensus, have not
                                                                              achieved significant policy action. Partnership for Prevention gathered
                                                                              leaders of these stakeholder groups to develop one consensus policy
                                                                              recommendation that, if passed, would move the needle on adult
         Vaccine Supply: A Manufacturer’s Perspective on Current              immunization. The expert panel surpassed its goal, producing six
17       Challenges and Opportunities
         D. Johnson
                                                                              recommendations.
                                                                                  This session will identify the specific recommendations, outline plans
         sanofi pasteur, Swiftwater, PA                                       to translate them into policy, and discuss how the stakeholders overcame
                                                                              their differences to achieve consensus.
    The vaccine enterprise in this country is a remarkable success story
that has resulted in freedom from disease for millions of children and        Reference:
adults. The existing system fundamentally works, and should be                1. Strengthening Adult Immunization: A Call to Action, Partnership for
strengthened and stabilized to improve the delivery of today’s vaccines,         Prevention, Washington, DC, 2005
as well as to bring forth a new generation of vaccines. Sanofi pasteur
proposed a number of actions to ensure a stronger U.S. vaccine supply
to the National Vaccine Advisory Committee in February 2002. Since
that time, these proposals have been conveyed to many stakeholders
involved in the vaccine enterprise. They include the need for the CDC
                                                                              19        Progress in the Field of Malaria Vaccinology
                                                                                        F. Dubovsky
                                                                                        Malaria Vaccine Initiative, Bethesda, MD
to receive additional funding to create and implement expanded vaccine
stockpiles; the inclusion of manufacturer expertise in formulating                There are multiple lines of evidence that assure the field that malaria
immunization policy; government and policy advisory boards acting             vaccines are technically feasible. In the recent past these experimental
with greater predictability; and strengthening outreach to convey the         scenarios have been partially replicated with vaccine constructs.
message that prevention is the most desirable intervention. There are         Classically malaria vaccinology has focused different immunologic
also practical steps that can strengthen vaccine predictability and supply,   effector mechanisms on different stages in the parasite life cycle. Pre-
including pay-for-performance incentives to physicians and increased          erythrocytic sterile immunity has been demonstrated with a prime-boost
vaccine reimbursement rates. We have made limited progress in the last        vaccine regime (Fowlpox/Modified Vaccinia Ankara bearing a string of
several years; government, policymakers, the health care community and        epitopes and the TRAP antigen) as well as recombinant proteins (a
industry still have much work ahead to sustain vaccine discovery,             mixed chimeric Hepatitis B virus-like-particle delivering CSP
development, production and stable supply.                                    formulated in an oil-in-water emulsion with QS21 and MPL – termed
                                                                              RTS,S/AS02). Impact on parasite density has been demonstrated under
References:                                                                   field conditions using a mixture of recombinant proteins delivered in a
1. CDC Program in Brief, Pediatric Vaccine Stockpiles, January 2004           water-in-oil emulsion (RESA, MSP2, MSP1 in Montanide ISA 720).
2. Institute of Medicine: Financing Vaccines in the 21st Century:             Globally there are many vaccine candidates that are being developed and
   Assuring Access and Availability, 2003                                     for the first time many of these candidates are using technologies that
3. National Vaccine Advisory Committee: Strengthening the Supply of           have the potential to be manufactured at industrial scale. A pilot proof-
   Routinely Recommended Vaccines in the United States,                       of-concept efficacy trial has completed with RTS,S/AS02 in 1-4 year old
   Recommendations From the National Vaccine Advisory Committee               children in Mozambique. Over the six month observation period the
   JAMA. 2003;290:3122-3128.                                                  vaccine was able to impact not only infection, but also clinical disease
4. Needs and Recommendations for the United States Poliovirus                 and severe disease.
   Vaccine Stockpile, Report of the Joint Working Group of the
   National Vaccine Advisory Committee (NVAC) and Advisory                    Reference:
   Committee on Immunization Practices (ACIP), National Vaccine               1. Alonso PL, Jahit S, Aponte JJ et al. Efficacy of RTS,S/AS02A vaccine
   Advisory Committee Meeting, February 3-4, 2004                                against Plasmodium falciparum infection and disease in young African
5. United States General Accounting Office, Report to Congressional              children: randomized controlled trial. Lancet 2004;364: 1411-1420
   Requesters: Childhood Vaccines: Ensuring an Adequate Supply Poses                                                                        (continued)


                                                                                                                                                     51
         Eighth Annual Conference
                                      ABSTRACTS OF INVITED PRESENTATIONS
         Novel and Classical Strategies for Attenuated Malaria Vaccines       Ballou WR, Thompson R, Cohen J. Efficacy of the RTS,S/AS02A
20       S. Kappe
         Seattle Biomedical Research Institute, Seattle, WA
                                                                              vaccine against Plasmodium falciparum infection and disease in
                                                                              young African children: randomised controlled trial. Lancet
                                                                              2004;364:1411 –20
    Malaria is transmitted by means of inoculation of the Plasmodium
parasite sporozoite stage during a mosquito bite. Sporozoites infect the
liver where they transform into liver stages, each developing into
                                                                                     Developing Adjuvants for Malaria Vaccines
thousands of first generation red blood cell infectious merozoites.
Using a mouse malaria model it was shown decades ago that
immunization with irradiated sporozoites completely protected against
                                                                            22       D. Heppner
                                                                                     Walter Reed Army Institute of Research, Silver Spring, MD
subsequent nonirradiated sporozoite challenge. This finding
demonstrated that sterilizing immunity against malaria infection is             The Malaria Vaccine Program at the Walter Reed Army Institute of
achievable. Experimental immunization of humans with irradiated             Research is developing a multi-antigen, multi-stage recombinant protein
sporozoites of human malaria parasites also conferred sterile protection    subunit-based vaccine intended to induce effective immune responses
thus making the liver stage a prime malaria vaccine target. However,        against pre-erythrocytic and blood stages of Plasmodium falciparum.
until recently the use of irradiated sporozoites as a malaria vaccine was   Although the immune correlates of vaccine-induced protection are not
considered impractical for a variety of reasons. We have recently shown     known, it is assumed that an effective subunit malaria vaccine will
in a mouse malaria model that inactivation of a single parasite gene        require a safe, potent adjuvant able to induce both a sustained cellular
arrests productive liver stage development and renders the parasite         and humoral immune responses against protective epitopes contained
unable to establish a blood stage infection. Immunization with              within soluble exogenous recombinant proteins. Additional selection
sporozoites of such attenuated parasites confers complete protection        criteria for a successful adjuvant include acceptable reactogenicity,
against infectious sporozoite challenge in mice. This protection is long    antigen compatibility, and overall stability of the antigen-adjuvant
lasting and stage-specific. We will discuss this new concept of a           formulation. Many adjuvants have been evaluated pre-clinically,
genetically attenuated malaria parasite vaccine and outline the possible    relatively few have been systematically evaluated in humans, and fewer
use for human vaccinations.                                                 yet in the context of clinical efficacy. Recently, the development of
                                                                            RTS,S/AS02A, a purified subunit-based malaria vaccine formulated
Reference:                                                                  with a novel adjuvant, illustrates the potential for an improved adjuvant
1. Mueller, A. K., Labaied, M., S. H. I. Kappe and K. Matuschewski          system to drive an effective immune response. Several adjuvants (CpG,
   (2005). Genetically modified Plasmodium parasites as a protective        oil-in-water emulsions, MPL, QS21 and others) will be reviewed in the
   live attenuated experimental malaria vaccine. Nature. 433, 164-167       context of recent malaria vaccine development with an emphasis on
                                                                            lessons learned from pre-clinical evaluations of candidate vaccines using
                                                                            non-human primate models


21       The Pathway Forward for Malaria Recombinant Vaccine (RTS,S):       Reference:
         Implications of Study Results                                      1. Heppner DG Jr, Kester KE, Ockenhouse CF, et. Al. Towards an
         W. Ballou                                                             RTS, S-based, multi-stage, multi-antiagen vaccine against falciparum
         GlaxoSmithKline Biologicals, Rixensart, Belgium                       malaria: progress at the Walter Reed Army Institute of Research.
                                                                               Vaccine 23 (17-18):2243-50, March 2005.
    Plasmodium falciparum is responsible for at least 300 million cases
of malaria each year and more than 1 million deaths, especially in
children under 2 years of age in sub-Saharan Africa. RTS,S/AS02A is a
                                                                                     Human Pailloma Virus Therapeutic Vaccines: Overview and
                                                                            23
candidate malaria vaccine that induces antibody and cellular immune
responses that inhibit the ability of malaria sporozoites to successfully            Underlying Immunology
infect humans. Efficacy reflected in both sterile immunity and/or a                  W. Kast
profound (>90%) reduction in infectious inoculum following                           University of Southern California, Los Angeles, CA
infectious mosquito challenge has been confirmed in field trials in
malaria-endemic regions. The most impressive data come from a                   Human papillomavirus (HPV) infection of cervical epithelium is
recently completed proof-of-concept trial in more than 2000 children        linked to the generation of cervical cancer. Although most women
aged 1-4 years in Mozambique, where significant vaccine efficacy            infected with HPV clear their lesions, the long latency period from
against infection, clinical malaria and severe malaria were observed. The   infection to resolution indicates that human papillomavirus evolved
next steps include determination of an optimal vaccination schedule in      immune escape mechanisms. Dendritic cells, targeted by vaccination
the target population (infants and children under 2), confirmation of       procedures, incubated with HPV virus-like particles induce an HPV-
vaccine safety and immunogenicity in infants, and implementation of         specific immune response. Langerhans cells located at the sites of
an appropriate Phase III program that could lead to vaccine licensure.      primary infection do not, implicating the targeting of Langerhans cells
                                                                            as an immune escape mechanism utilized by HPV. Langerhans cells
Reference:                                                                  incubated with HPV virus-like particles upregulate the PI3K pathway
1. Alonso PL, Sacarlal J, Aponte JJ, Leach A, Macete E, Milman J,           and down regulate MAPK pathways. With the inhibition of PI3K and
   Mandomando I, Spiessens B,Guinovart C, Espasa M, Bassat Q, Aide          incubation with HPV virus-like particles, Langerhans cells initiate a
   P, Ofori-Anyinam O, Navia MN, Corachan S, Ceuppens M, Dubois             potent HPV-specific response. PI3K activation in Langerhans cells
   MC, Demoitié MA, Dubovsky F, Menéndez C,Tornieporth N,                   defines a novel escape mechanism utilized by HPV. Apart from these
                                                                            fundamental HPV immunological data an overview w ill be given of the


52
   on Vaccine Research
                                       ABSTRACTS OF INVITED PRESENTATIONS
current developments in the field of preventive and therapeutic vaccines    the biologic and clinical implications of these findings will be presented
against HPV.                                                                and discussed at the meeting.

References:                                                                 Reference:
1. Brinkman JA, Caffrey AS, Muderspach LI, Roman LD and Kast                1. Masliah E, Hansen L, Adame A, Crews L, Bard F, Lee C, Seubert P,
   WM: The impact of anti HPV vaccination on cervical cancer                   Games D, Kirby L, Schenk D (2005) Abeta vaccination effects on
   incidence and HPV induced cervical lesions: Consequences for                plaque pathology in the absence of encephalitis in Alzheimer disease.
   clinical management. Eur J Gyn Onc, In Press, 2005.                         Neurology 64:129-131.
2. Fausch SC, Fahey LM, Da Silva DM and Kast WM: HPV can escape
   immune recognition through Langerhans cell PI3-kinase activation, J
   Immunol, In Press, 2005.
3. Da Silva DM and Kast WM: Vaccination against cervical cancer:
   hopes and realities. Am J Cancer, In Press 2005.                         26        Vaccines for Type 1 Diabetes
                                                                                      R. Insel
                                                                                      Juvenile Diabetes Research Foundation International, New York, NY

                                                                                Type 1 (or insulin-dependent) diabetes is an autoimmune disease
                                                                            associated with cell-mediated immune destruction of the insulin-
24       Hepatitis C Therapeutic Vaccines
         M. Houghton
         Chiron Corporation, Emeryville, CA
                                                                            producing beta cells of pancreatic islets. Approximately 16,000
                                                                            childhood cases of type 1 diabetes occur annually in the United States, a
                                                                            rate similar to that of several infectious diseases for which vaccines have
                                                                            been developed and licensed. Both genetic and environmental risk
    There is evidence that the liver disease associated with persistent
                                                                            factors contribute to disease, whose incidence has been increasing for at
infection by the hepatitis C virus (HCV) is modulated by both humoral
                                                                            least the last four to five decades. The period between initial insulitis
and cellular immune responses to the virus and that response to
                                                                            and sensitization to beta cell antigens and the onset of overt, clinical
antiviral therapy is also predicated by such immune responses. It follows
                                                                            diabetes is quite variable, resulting in a large pool with prediabetes.
therefore that boosting of viral immunity by appropriate vaccination
                                                                                Primary prevention with vaccines targeted at environmental factors
could be of therapeutic value, particularly when given as adjunct
                                                                            is not currently possible. Secondary prevention with vaccines after the
therapy with antivirals. To this end, a clinical program is underway
                                                                            disease process has commenced is being explored in both the at-risk
designed to boost both HCV-specific humoral and cellular immune
                                                                            setting, to prevent the onset of diabetes, and the recent-onset diabetes
responses in chronically-infected HCV patients using vaccine
                                                                            setting, to preserve functional beta cell mass. Current vaccine
monotherapy and combination vaccine and antiviral therapies. It is
                                                                            approaches are targeted at altering function of pathogenic effector T
hoped that use of recombinant envelope glycoprotein gpE1/gpE2
                                                                            cells and inducing lasting immunologic tolerance or immunoregulation
vaccine formulations will boost cross-neutralising antibody titers and
                                                                            to beta cell antigens. Beta cell antigen-specific approaches under
thus help to control disease progression and response to antiviral
                                                                            investigation include presentation of beta cell antigens by tolerogenic
therapy while an ISCOM-adjuvanted polyprotein formulation may
                                                                            routes (oral, intranasal), in tolerogenic forms (peptides, altered peptide
boost broadly cross-reactive CD4+ and CD8+ T cell responses to the
                                                                            ligands), on tolerogenic cells (resting dendritic cells) or with co-
virus with similar benefits. Supporting pre-clinical data for these
                                                                            stimulatory blockade. Islet cell antigens used in vaccines have included:
experimental approaches will be presented along with the status of the
                                                                            insulin, proinsulin, insulin B chain or peptides (B:9-23), glutamic acid
clinical development pathway.
                                                                            decarboxylase (GAD65), and heat shock protein 60 (Hsp60)-derived
                                                                            peptides (p277). Antigen non-specific approaches include the use of
Reference:
                                                                            FcR nonbinding anti-CD3 monoclonal antibody (anti-CD3 Ab), which
1. Hsu HH, Abrignani S & Houghton M. Prospects for a Hepatitis C
                                                                            can induce lasting remission of diabetes in nonobese diabetic (NOD)
   Vaccine. Clin Liver Dis. 3(4) : 901-915, 1999
                                                                            mice that is associated with the generation of regulatory T cells. Short-
                                                                            term administration of humanized FcR nonbinding anti-CD3 Ab in
                                                                            newly diagnosed human type 1 diabetes preserves residual beta cell
                                                                            function for over a year, as evidenced by a decrease in the rate of loss of
25       Immunotherapy as a Treatment Possibility for Alzheimer’s Disease
         D. Schenk
         Elan Pharmaceuticals, South San Francisco, CA
                                                                            insulin production, improved glycemic control, and concomitant
                                                                            reduction of insulin dosing. To augment and prolong the effect, anti-
                                                                            CD3 Ab will be evaluated when administered for multiple courses,
                                                                            simultaneously with islet antigens, or with beta cell regeneration
    The idea of immunizing patients suffering from an amyloidosis with
                                                                            therapeutics. In general, vaccine development for type 1 diabetes will be
the offending monomer has emerged as a novel strategy to treat a
                                                                            accelerated by the identification of human beta cell T cell epitopes,
number of diseases including Alzheimer’s. The basis for such an
                                                                            improved approaches in quantifying pathogenic autoantigen-reactive
approach is that beta amyloid peptide is an unusual byproduct of a
                                                                            effector T cells and protective regulatory T cells, and the generation of
much larger precursor protein, that once cleaved out, readily forms
                                                                            surrogate markers for therapeutic effects. A robust infrastructure for
amyloid fibrils that accumulate in the brain tissue of Alzheimer’s
                                                                            developing and evaluating type 1 diabetes vaccines currently exists
patients and are thought to cause cognitive dysfunction as a result of
                                                                            through support of multiple funding agencies, including JDRF.
neuronal stress and eventually death. By
    immunizing with beta amyloid peptide or its fragments, either           References:
actively or passively, antibodies generated to it evidently appear to       1. Raz I, Eldor R, Naparstek Y. Immune modulation for prevention of
disrupt the amyloidogenic process and result in reduced plaque lesions         type 1 diabetes mellitus. Trends Biotechnol. 2005 Mar;23(3):128-34
in both animal models and in patients suffering from the disease. Both                                                                   (continued)


                                                                                                                                                          53
         Eighth Annual Conference
                                        ABSTRACTS OF INVITED PRESENTATIONS
2. Chatenoud L. Anti-CD3 antibodies: towards clinical antigen-specific                  Innate Imprinting and Inflammatory Lung Disease
   immunomodulation. Curr Opin Pharmacol. 2004 Aug;4(4):403-7.
   Review
                                                                               29       T. Hussell
                                                                                        Imperial College London, London, England
3. Bluestone JA, Tang Q. Therapeutic vaccination using CD4+CD25+
   antigen-specific regulatory T cells. Proc Natl Acad Sci U S A. 2004             Immune responses to infectious disease need to be regulated to
   Oct 5;101 Suppl 2:14622-6. Review.                                          prevent bystander tissue damage. Regulation is carefully orchestrated in
                                                                               organized lymphoid tissue such as lymph nodes but less so in sites where
                                                                               compartmentalization of immune cells is not as apparent. The lung is a
                                                                               classic example of a site where inflammation is not regulated (the site of

27        Limitations of B-cell Responses in Early Life
          C. Siegrist
          University of Geneva, Geneva, Switzerland
                                                                               asthma, pneumonia and bronchiolitis). Lower respiratory tract viral
                                                                               infections recruit a vast inflammatory infiltrate that, in clearing the
                                                                               virus, occlude the airways. In addition, inflammatory cells release
                                                                               mediators such as TNF that act on distant organs to cause the life
    Early immunization is required to induce immunity against diseases         threatening clinical symptoms of wasting, weight loss, fever and appetite
that may occur very early in life. This is however limited by the relative     suppression. One therapeutic strategy would involve the induction of
immaturity of the immune system. Vaccine antibody responses increase           regulation at this vulnerable site. We show that the lung
with age in a step-wise manner, such that only the most immunogenic            microenvironment can be educated to respond to a variety of infections
vaccines show significant protective efficacy after a single infant dose.      in a more controlled manner by instilling toll-like receptor ligands or
Murine models assessing neonatal responses to human infant vaccines            immunogenic proteins derived from bacteria such as LTK63. We have
indicated that this reflects a stepwise increase in Germinal Center            named this procedure “innate imprinting”, which is long lasting and
reactions, limited by the delayed postnatal development of follicular          provides generic protection against a variety of serious lower respiratory
dendritic cells. Another hallmark of early life responses are the short        tract infections.
persistence of vaccine antibodies. This reflects in mice a limited capacity
of the neonatal bone marrow to support the establishment of long-lived         Reference:
plasma cells: plasmablasts efficiently migrate to the early life bone          1. Williams, A.E., Edwards, L., Humphreys,I.R., Snelgrove, R., Rae, A.,
marrow, but fail to receive appropriate differentiation / survival signals.       Rappuoli, R. and Hussell, T. “Innate imprinting by the modified
Importantly, factors limiting the magnitude and duration of infant                heat-labile toxin of Escherichia coli (LTK63) provides generic
responses do not prevent efficient priming, such that neonatally-                 protection against lung infectious disease”. J Immunol. 173 (2004),
triggered immune memory may be readily recalled later in life.                    7435-43.
Unfortunately, however, immune memory is not sufficient to confer
full protection against pathogens requiring neutralizing antibodies
either at the infection site (RSV, influenza) or rapidly after exposure
(encapsulated bacteria), and these remain major threats to young infants.               Interrogating and Exploiting Memory B Cells

Reference:
                                                                               30       A. Lanzavecchia
                                                                                        Institute for Research in Biomedicine, Bellinzona, Switzerland
1. Lambert P.H., Liu M. and C.A. Siegrist, Can successful vaccines teach
   us how to induce efficient protective immune responses? Nature                  Our current interest is to understand the mechanisms that control B
   Medicine, April 5, 2005 (in press)                                          cell priming and maintenance of memory B cells and serum antibody
                                                                               levels. We developed a new strategy for the purification of human naïve
                                                                               B cells that was instrumental to determine their activation requirements
                                                                               and in vivo turnover. We found that, in order to undergo clonal

28        Recent Advances in Studies of B and T cell Responses Early in Life
          J. Crowe
          Vanderbilt University, Nashville, TN
                                                                               expansion and differentiation, naïve B cells require, in addition to BCR
                                                                               stimulation and cognate T cell help, a third signal delivered by microbial
                                                                               products through Toll like receptors. In contrast, memory B cells can
                                                                               proliferate and differentiate in response to polyclonal stimuli such as
    This talk will review the evidence that the antibody response made         bystander T cell help, TLR agonists and homeostatic cytokines.
by infants in response to viral infection or vaccination is of low             Consistent with these different activation requirements is the
magnitude and poor quality. Using molecular studies of the human               observation that human memory B cells spontaneously turn over at high
infant response to two major common viral pathogens of infancy,                rate in vivo, while naïve B cells do not. To gain insights into the
respiratory syncytial virus and rotavirus, we will explore the molecular       mechanisms that sustain the serological response we monitored plasma
basis for poor quality infant antibodies. The talk will emphasize the role     cell generation, serum antibodies and frequency of memory B cells in
of somatic hypermutation in enhancing the antiviral function of                donors boosted with tetanus toxoid. The results are consistent with a
antibodies, and the poor ability of infants to introduce mutations into        two phase model in which a short antigen-driven phase of plasma cell
antibody gene sequences following primary infection or vaccination.            generation sustains high antibody levels for 6 to 8 months. This is
                                                                               followed by a low level sustained plasma cell generation through
Reference:                                                                     homeostatic mechanisms that maintain for a lifetime constant antibody
1. Weitkamp JH, Kallewaard N, Kusuhara K, Bures E, Williams JV,                levels proportional to the frequency of memory B cells. A mathematical
   LaFleur B, Greenberg HB, Crowe JE Jr. Infant and Adult Human B              model of the serological response has been developed and will be
   Cell Responses to Rotavirus Share Common Immunodominant                     discussed in the context of vaccination strategies. Because of their
   Variable Gene Repertoires. Journal of Immunology 2003; 171:                 capacity of self renewal memory B cells represent a repository of
   4680-8.                                                                     potentially useful antibodies which have been selected in the course of


 54
   on Vaccine Research
                                      ABSTRACTS OF INVITED PRESENTATIONS
an immune response to human pathogens. We developed an improved                1 vaccine research field although numerous interesting research
method of immortalization of human memory B cells and used it to               strategies are being devised and tested. Our current efforts towards this
isolate from a patient recovered from SARS coronavirus infection several       objective will be summarized.
monoclonal antibodies specific for different viral proteins, including 35
antibodies with potent neutralizing activity. These results show that it is    Reference:
possible to interrogate the memory repertoire of immune donors to              1. Shiver JW, Emini EA. Recent advances in the development of HIV-1
rapidly and efficiently isolate neutralizing antibodies which have been           vaccines using replication-incompetent adenovirus vectors. Annu
selected in the course of natural infection.                                      Rev Med. 2004;55:355-372.




31        The Use of MVA as a Vaccine Delivery Vector to Elicity Protective
          Immune Responses Against Pathogens                                   33       Development of Novel Vaccine Candidates Using Directed
                                                                                        MolecularEvolution
          H. Robinson                                                                   C. Locher
          Emory University, Atlanta, GA                                                 Maxygen, Inc., Redwood City, CA

    The development of an HIV/AIDS vaccine faces a number of                       Directed molecular evolution strategies include DNA shuffling
challenges including the genetic diversity of the virus, the poor ability of   methods, such as multi-gene and synthetic shuffling, to create large
the virus to be seen by neutralizing Ab, and the ability of the virus to       libraries of genetically recombined molecules. Chimeric molecules from
persist in the presence of a strong immune response. Heterologous              these libraries are then screened for improved characteristics. More
prime/boost immunization regimens have the potential for raising high          effective vaccines can be developed because chimeras are selected for
levels of both T cell and Ab responses. Working with collaborators at          improved immunogenicity and increased reactivity to multiple antigenic
the Emory Vaccine Center, the NIH and the CDC, we have developed               variants. Genetically recombined chimeric molecules can also have
single moiety Gag-Pol-Env expressing DNA and MVA vaccine vectors.              increased recombinant polypeptide expression through substitution of
These vaccines elicit a broad T cell response, good titers of anti-Env Ab      hydrophilic/acidic amino acid residues. Moreover, increased viral growth
and have provided long term control of a virulent SHIV challenge in the        kinetics (for improved inactivated or live attenuated viral vaccine
macaque model. Macaques with controlled infections have stable low-            manufacturing) is another application. These technologies have been
levels of CD8 and CD4 T cells that co-produce IFN-_ and IL-2. The              used to create chimeric dengue virus vaccine antigens that generate
vaccine is currently in early stage human trials.                              neutralizing antibodies to all four serotypes; chimeric hepatitis B virus
                                                                               surface antigens with improved immunogenicity; chimeric HIV-1
Reference:                                                                     envelope antigens that induce neutralizing antibodies against multiple
1. Amara RR, Villinger F, Altman JD, Lydy SL, O’Neil SP, et al:                strains of viruses; improved Venezuelan equine encephalitis virus
   Control of a Mucosal Challenge and Prevention of AIDS in Rhesus             envelope vaccine antigens; and improved chimeric Plasmodium
   Macaques by Multiprotein DNA/MVA Vaccine. Science 292:69-74.                falciparum Erythrocyte Membrane Protein-1 (PfEMP-1) antigens that
   Published online March 8, 2001; 0.1126/science.1058915.                     induce antibodies to multiple antigenic variants of the malaria parasite.
                                                                               Directed molecular evolution strategies have also been used to develop
                                                                               more potent adjuvants that are co-administered with vaccine candidates.
                                                                               Statistical analyses of multiple amino acid substitutions imparting

32        Strategies for HIV Vaccine Development
          J. Shiver
          Merck and Company, Inc, West Point, PA
                                                                               improved characteristics and repeated DNA shuffling may lead to
                                                                               further improvements of vaccine efficacy.

                                                                               Reference:
    Despite the critical need for a vaccine to prevent HIV-1 infection,        1. Locher, C.P., M. Paidhungat, R. Whalen, and J. Punnonen. 2005.
development of an effective vaccine remains elusive. Research has                 DNA Shuffling and Screening Strategies for Improving Vaccine
increasingly focused on evaluating whether a vaccine based on eliciting           Efficacy. DNA and Cell Biology 24(4):256-263.
T cell immunity against HIV-1 could control or prevent infection.
This work is reflected in the large number of clinical trials currently
evaluating vaccines that elicit cellular immunity against HIV-1. We
developed a strategy for vaccine development comprised of two
components: (i) determine the best means for inducing cellular
immunity by comparing different vaccine approaches in animal
                                                                               34       ChimeriVaxTh: A Novel Platform for Genetically
                                                                                        Engineered Live Viral Vaccine
                                                                                        T. Monath
immunization studies; and (ii) identify which HIV-1 proteins are the                    Acambis, Inc., Cambridge, MA
best antigens for T cell immune responses by studying cellular immune
responses of HIV-infected subjects. Based on these studies DNA and                 A number of platform technologies for new vaccine development
replication-defective adenovirus vector vaccines were selected for testing     have been explored, and a few have shown promise in clinical trials.
in clinical trials. The adenovirus vector will be tested in a proof-of-        One of the most promising approaches utilizes live, recombinant viruses
concept clinical trial to determine the effectiveness of this vaccine.         which express one or more foreign genes encoding the antigen(s) of
Ongoing efforts also focus on developing an antigen that can elicit            interest. We have used yellow fever (YF) 17D as a vector platform for
neutralizing antibodies against HIV-1. Such antibody responses should          creating new recombinant vaccines against West Nile (WN), Japanese
be clinically relevant, i.e., able to potently neutralize diverse primary      encephalitis (JE), and dengue (DEN) viruses. Construction of the
viral isolates. Efforts have stalled on this objective throughout the HIV-                                                                  (continued)


                                                                                                                                                    55
         Eighth Annual Conference
                                      ABSTRACTS OF INVITED PRESENTATIONS
vaccines involved infectious clone technology, in which the prM-E genes
of YF 17D are replaced with the corresponding donor genes of the
vaccine target. In the case of the WN and JE vaccines, mutations
inserted in the E gene were inserted to establish an improved attenuated
phenotype. The chimeric vaccines have reduced virulence compared to
parental YF 17D vaccine, yet elicit strong neutralizing antibody levels
specific to the donor gene. The vaccine candidates protect monkeys
against challenge with wild-type JE, WN or dengue viruses.
ChimeriVax™ vaccines against WN, JE and dengue have entered
clinical trials. In Phase 1 and 2 trials they have proven to be well
tolerated and highly immunogenic, without restriction by preexisting
immunity to the vector (yellow fever). In addition a chimeric WN
vaccine is in the late stages of development for protection of horses. The
presentation will provide an update on the status of preclinical and
clinical development of these new vaccines.

References:
1. Lai CJ and Monath TP. Chimeric flaviviruses: novel vaccines against
   dengue fever, tick-borne encephalitis, and Japanese encephalitis. In
   Chambers TJ and Monath TP (eds). The Flaviviruses: Detection,
   Diagnosis, and vaccine Development. Adv Virus
2. Pugachev K, Monath TP, Guirakhoo F. Chimeric vaccines against
   Japanese encephalitis, dengue and West Nile. In Levine M et al (Eds)
   New Generation Vaccines, 3rd Edit, Marcel Dekker, New York, 2004,
   pp. 559-71.




 56
on Vaccine Research




   ABSTRACTS OF
 ORAL SUBMITTED
  PRESENTATIONS




                      57
        Eighth Annual Conference
                              ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
         Lipotechoic Acid Conjugate Vaccine for Staphylococcus                        Pertussis and tetanus antibody GMTs were comparable; anti-diphtheria
S1       A. Lees, J. KoKai-kun, A. LopezAcosta, J. Acevedo, J. Mond
         Biosynexus Inc, Gaithersburg, MD.
                                                                                      levels were lower after the lower diphtheria content Tdap. Conclusions:
                                                                                      Tdap is less reactogenic than DTaP-IPV without inferior
                                                                                      immunogenicity.
    Staphylococcus is an opportunistic, Gram-positive bacterial genus
that is increasingly becoming antibiotic resistant. Lipotechoic acid                  References:
(LTA) is a common and obligatory element of Gram-positive                             1. National Advisory Committee on Immunization. Canadian Guide to
bacteria; no LTA deficient mutants are known. LTA from many                              Immunization. Ottawa, ON: Health Canada. 2002.
species have poly(glycerolphosphate) (PGP) as a common structural                     2. Rennels MB. Pediatrics 2000; 105;e12.
element, although it is often decorated with D-alanine and
carbohydrate. A protective antibody to S. epidermidis LTA, A110, is
being evaluated in clinical trials for its ability to protect against
                                                                                                An Antigen-Antibody Complex-based Therapeutic Vaccine for
                                                                                      S3
Staphylococcus bacteria. A110 crossreacts with LTA from bacteria
containing PGP LTA but not Gram-positive bacteria that contain                                  Chronic Hepatitis B Patients
nonPGP LTA. A110 also reacted with deacylated S. aureus LTA                                     Y. Wen1, D. Xu2, Z. Yuan1, K. Zhao3
(DeAcLTA), which has been stripped of its pendant D-alanines and                                1
                                                                                                  Department of Medical Molecular Virology, Shanghai Medical College, Fudan
fatty acids. Both LTA and DeAcLTA are poorly immunogenic in                                     University, Shanghai, CHINA, 2Dept.Infectious Diseases, Di Tan Hospital,
mice. DeAcLTA was oxidized, functionalized with a mercapto-                                     Beijing, CHINA, 3Beijing Institute of Biological Product, Beijingi, CHINA.
amino-oxy reagent and subsequently linked to maleimide derivatized-
tetanus toxoid (TT). Due to the extreme negative charge on the                            Yeast derived hepatitis B surface antigen complexed to anti-HBs
DeAcLTA, the highest levels of coupling were obtained under                           proved effective in treating HBsAg positive transgenic mice. This
relatively acidic pH. Unlike the unconjugated antigen, the DeAcLTA-                   complex increased uptake of HBsAg by antigen presenting cells and
TT conjugate vaccine induced high levels of anti-LTA IgG                              modulated processing and presentation of HBsAg. In stage I phase I
antibodies. The response was boostable, indicating conversion of the                  clinical trial 22 healthy volunteers were vaccinated with three doses of
DeAc LTA from a T-cell independent to a T-cell dependent antigen.                     30_g, 60_g and 90_g of HBsAg in the complex at 4-week intervals. In
The antibodies cross reacted with intact LTA. Furthermore, the sera                   stage II phase I clinical trial, 9 volunteers received 90_g of HBsAg for 6
were highly protective in an opsophagocytic assay against S.                          injections. The renal, liver function and blood chemistry tests were all
epidermidis bacteria. Because PGP is a common element of most                         within the normal range and all recipients developed high titer of anti-
Gram-positive bacteria, this conjugate vaccine has promise for                        HBs.. In phase IIA clinical trial, 36 chronic hepatitis B patients were
providing broad protection.                                                           vaccinated with 60_g , 90_g of HBsAg or adjuvant for six injections.
                                                                                      Around 30% of the treated patients showed a 2-4 log decrease in serum
                                                                                      HBV DNA and some were sero-converted from HBeAg strong positive
                                                                                      and anti-HBe negative to coexistence of anti-HBe positive and HBeAg
         Adult Formulation Tetanus and Diphtheria Toxoids with Acellular              weak positive. In two treated patients anti-HBs was detected, but with
S2       Pertussis Vaccine (Tdap) has Comparable Immunogenicity but
         Less Reactogenicity than DTaP-IPV for the Pre-school, Fifth-
                                                                                      no significant changes in their HBeAg or serum HBV DNA status.
                                                                                      Patients that had a decrease in serum HBV DNA showed “flares” in
         dose Booster                                                                 their liver function assays, but returned to normal limits later. While
         J. M. Langley1, S. A. Halperin1, E. Mills2, A. Tomovici2, R. Guasparini3,    this therapeutic vaccine is effective for certain chronic hepatitis B
         G. Predy4, B. Law5, F. Diaz-Mitoma6, P. Whitsitt7, B. Tapiero8, M. Dionne9   patients, the contradictions and indications of this vaccine will be
         1
           Dalhousie University, Halifax, NS, CANADA, 2Sanofi-Pasteur, Toronto, ON,   studied.
         CANADA, 3TASC Research, Surrey, BC, CANADA, 4Capital-Health, Edmonton,
         AB, CANADA, 5Univ-Manitoba, Winnipeg, MB, CANADA, 6CHEO, Ottawa, ON,         References:
         CANADA, 7Paradigm Clin Trials, Oshawa, ON, CANADA, 8Hop-Ste-Justine,         1. Zheng BJ, Ng MH, He LF, et al. Therapeutic efficacy of hepatitis B
         Montreal, PQ, CANADA, 9CHUQ, Beauport, PQ, CANADA.                              surface antigen-antibodies-recombinant DNA composite in HBsAg
                                                                                         transgenic mice. Vaccine 2001; 19:4219-4225.
    Background: The pre-school (4-6 year), fifth-dose booster with                    2. Zheng BJ, Zhou J, Qu D, et al. Selective functional deficit in
DTaP-IPV is associated with increased injection site reactions,                          dendritic cell-T cell interaction is a crucial mechanism in chronic
perhaps related to pertussis antigen content. Methods: Healthy                           hepatitis B virus infection. J Viral Hepat 2004; 11:217-214.
children age ≥ 4 to <7 years with completed primary series and 4th
dose of DTaP-IPV-Hib (Pentacel™) were randomized to Tdap
followed by IPV 4-6 weeks later, or DTaP-IPV (Quadracel™).
Results: 593 children were enrolled at 8 sites. Safety endpoints days
0-14 were less frequent in the Tdap group than the DTaP-IPV group:
erythema (34.6 v. 51.7%), swelling (24.2 v. 33.8%), pain (39.6 v.
                                                                                      S4        Different Immune Response after Sequential Use of Pneumococcal
                                                                                                Polysaccharide and Pneumococcal Conjugate Vaccine
                                                                                                A. de Roux1, B. Schmoele-Thoma2, N. Ahlers2, W. Gruber3, G. Siber3,
67.2%) and fever (8.7 v. 16.9%). 100% (95% CI 98.6, 100) of                                     D. Sikkema3, T. Welte4, H. Lode1
participants had seroprotective antibody levels to diphtheria and                               1
                                                                                                  Heliosklinik Emil-von-Behring, Berlin, GERMANY, 2Wyeth, Muenster, GERMANY,
tetanus at 4-6 weeks (≥ 0.10 IU/ml). The Tdap v. DTaP-IPV 4-fold                                3
                                                                                                  Wyeth, Pearl River, NY, 4University Hannover, Hannover, GERMANY.
antibody rise was: pertussis toxoid 91.9% (95% CI 87.9, 94.9) v.
96.8% (93.8, 98.6), filamentous hemagglutinin 88.1% (83.6, 91.8)                         Background: Pneumococcal conjugate vaccine (7vPnC) in adults
v. 92.8 (88.9, 95.7), pertactin 94.3% (90.7, 96.7) v. 92% (88.0,                      may complement the polysaccharide vaccine (23vPS). This study
95.1) and fimbriae 94.6% (91.2, 97.0) v. 87.6% (82.9, 91.5).                          examined the immunogenicity of conjugate administered before or after


58
  on Vaccine Research
                                  ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
polysaccharide. Methods: 217 individuals aged ≥ 70 years without                               time that the chemokine receptor- targeted antigens are degraded by
prior pneumococcal immunization were equally randomized in an open                             proteosomes and efficiently cross-presented to MHC class I. The
label study to receive either 7vPnC (Prevnar® 2µg saccharide/dose,                             strategy we developed is very simple and potent. Protein or DNA
except 4µg for 6B, Wyeth), or 23vPS (Pneumovax®23, 25µg                                        immunizations elicit therapeutic antitumor immunity against wide
saccharide/dose, Aventis Pasteur MSD). One year later, 7vPnC                                   variety of tumors, which express non-immunogenic or weakly
recipients received 23vPS and 23vPS recipients received 7vPnC. Blood                           immunogenic tumor antigens, such as a recently discovered embryonic
samples were obtained prior to and one month post vaccination.                                 antigen OFA. In addition, use of chemokines also allows induction of
Antibody responses (GMCs) were measured by ELISA. Results: After                               controlled and polarized immune responses individually tailored for the
initial 7vPnC, GMCs of all serotypes, except 19F (non-inferior), were                          specific disease at will.
superior to initial 23vPS. 7vPnC/ 23vPS recipients had higher GMCs
(point estimates) compared to 23vPS alone. 23vPS/7vPnC recipients                              References
had lower GMCs compared to 7vPnC alone.                                                        1 Biragyn A, Tani K, Grimm MC, Weeks S, Kwak LW. Genetic fusion
                                                                                                  of chemokines to a self tumor antigen induces protective, T-cell
Pneumococcal ELISA GMCs (µg/ml) with 95% CI, All Available                                        dependent antitumor immunity. Nat Biotechnol 1999; 17(3):253-
Immunogenicity Population                                                                         258.
                                                                                               2. Biragyn A, Ruffini PA, Coscia M, Harvey LK, Neelapu SS, Baskar S,
Serotypes\                                                                                        Wang JM, Kwak LW. Chemokine receptor-mediated delivery directs
Treatments      N     4        6B         9V         14         18C        19F      23F           self-tumor antigen efficiently into the class II processing pathway in
7vPnC           110   3.1      8.0       9.8       17.1       13.0       5.5      12.4            vitro and induces protective immunity in vivo. Blood 2004;
                      2.2, 4.3 6.0, 10.8 7.5, 12.8 12.3, 24.0 10.1, 16.7 4.1, 7.4 9.0, 17.0       104(7):1961-1969.
7vPnC/23vPS 36        2.0      5.4        5.7        14.5      7.6       8.4       7.4
                      1.2, 3.5 3.3, 9.0   3.6, 8.9   8.8, 23.9 5.2, 11.1 5.3, 13.1 4.0, 13.6


                                                                                               S6
23vPS           107   1.4      4.4        3.6        8.5       6.8         4.4      3.8                 Directed Molecular Evolution Creates HIV-1 Novel gp120 Variants
                      1.1, 2.0 3.4, 5.8   2.8, 4.6   6.0, 12.1 5.2, 8.9    3.4, 5.8 2.9, 5.0
                                                                                                         That Induce Broadly Neutralizing Antibodies in Rabbits
23vPS/7vPnC 78        0.9      2.2        3.0        6.7        5.1        2.1      3.0                  L. Xu, X. Du, R. Whalen
                      0.6, 1.3 1.5, 3.2   2.2, 4.0   4.5, 9.9   3.7, 6.8   1.5, 3.0 1.9, 4.8             Infectious Diseases, Maxygen, Inc., Redwood City, CA.

Conclusion: In pneumococcal vaccine-naïve individuals aged ≥ 70                                    Background: Attempts to develop a preventative vaccine to HIV-1
years, 7vPnC induces a superior immune response to 23vPS for six of                            capable of inducing neutralizing antibodies have been hindered by the
seven 7vPnC serotypes and appears to increase antibody response to                             lack of appropriate immunogens. We hypothesize that directed
subsequent 23vPS. However, initial 23vPS may induce                                            molecular evolution can create novel Envelope variants that render
hyporesponsiveness as measured by decreased antibody responses to                              existing neutralizing epitopes more immunogenic. Methods: In vitro
subsequent 7vPnC.                                                                              homologous DNA recombination was used to create novel chimeric
                                                                                               variants of the Env protein from wild-type env sequences encoding clade
Reference:                                                                                     B gp120 and gp120 Core. Variants were characterized by the binding of
1. Kuhnke A, Lode H, De Roux A, Ahlers N, Thoma B, Madore D,                                   human monoclonal antibodies. Rabbits were immunized with plasmid
   Welte T. Comparison of immunogenicity of pneumococcal                                       DNA using electroporation followed by boosting with a heterologous
   conjugate (PnC) and 23-valent polysaccharide vaccine (23vPS) in                             adjuvanted gp120 protein. Sera and purified IgG were used to measure
   elderly patients. ICAAC 2004; G-1675-2004.                                                  neutralization activity using a pseudovirus entry assay. Results:
                                                                                               Chimeric variants created by in vitro recombination exhibited novel
                                                                                               antigenicity, based on antibody binding, with respect to the parental
                                                                                               genes from which they were derived. Analysis of the neutralization

S5           Induction of Therapeutic Antitumor Immunity via Chemokine                         activity of antibodies induced by the variants using a panel of
             Receptor Mediated Antigen Cross-Presentation.                                     pseudoviruses derived from primary clade B and non-clade B viruses
             A. Biragyn, D. Baatar, R. Schiavo                                                 showed that gp120 variants presented improved neutralization activity.
             Laboratory of Immunology, GRC, National Institute on Aging, Baltimore, MD.        Neutralization activity induced by chimeric gp120Core sequences was
                                                                                               also greater than that given by a parental gp120Core. Conclusion: These
    We have recently established a novel strategy for rendering weakly                         results indicate that the use of directed molecular evolution can improve
or non-immunogenic self tumor antigens immunogenic. The strategy is                            the immunogenicity of the HIV-1 Env protein.
based on use of proinflammatory chemokines to deliver antigens to
immature DCs through targeting chemokine receptors differentially                              References:
expressed on APCs. Herein, we report that chemokine receptor                                   1. Mascola JR. Defining the protective antibody response for HIV-1.
mediated targeting is an efficient strategy to cross-present antigens to                          Curr Mol Med 2003; 3:209-216.
elicit potent CD4+ and CD8+ responses. The mechanism by which the                              2. Locher CP, Soong NW, Whalen RG, Punnonen J. Development of
fusions elicit responses is efficient uptake, processing and presentation                         novel vaccines using DNA shuffling and screening strategies. Curr
of antigens via the MHC pathways. Experiments with inhibitors of                                  Opin Mol Ther 2004; 6:34-39.
intracellular trafficking suggest that chemo-attractant fusion proteins,
but not antigen alone, were processed and presented through early/late
endosomal and Golgi compartments, and stimulated antigen-specific T
cells both in vitro and in vivo. Moreover, our data indicate for the first                                                                                    (continued)


                                                                                                                                                                     59
        Eighth Annual Conference
                             ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
         The Human Hookworm Vaccine Initiative (HHVI): Progress                         clinical hallmark of hookworm disease is iron deficiency anemia, which
S7       in the Product Development and Testing of the Na-ASP-2
         Hookworm Vaccine
                                                                                        is influenced by numerous other factors (e.g., background nutritional
                                                                                        status, co-infections, etc). Finally, the marked heterogeneity of
         M. E. Bottazzi1, J. Bethony1, S. Brooker2, G. Goud1, A. Loukas3, S. Mendez1,   hookworm infections in endemic areas, including over-distribution of
         B. Zhan1, K. Stoever4, P. Hotez1                                               infection in community (such that a minority of people harbor a
         1
           Microbiology and Tropical Medicine, The George Washington University,        majority of the infection), marked geographic variation, age-related and
         Washington, DC, 2London School of Hygiene and Tropical Medicine, London,       gender-related differences in prevalence and intensity of infection are
         UNITED KINGDOM, 3Queensland Institute of Medical Research, Brisbane,           further obstacles in designing and evaluating the efficacy of a
         AUSTRALIA, 4Human Hookworm Vaccine Initiative, Sabin Vaccine Institute,        hookworm vaccine.
         Washington, DC.                                                                     Methods: Worm burden is a key determinant of hookworm
                                                                                        morbidity and transmission dynamics. Hence, a reduction in worm
    Background: Human hookworm infection, a leading cause of iron-                      burden is an appropriate measure of vaccine efficacy. In this context,
deficiency anaemia and malnutrition, affects 740 million people in                      vaccine efficacy has been defined as 1-(AWV/AWU), where AWU and
developing countries of the tropics. Currently, the major approach to                   AWV are the average (arithmetic mean) worm burdens in the
hookworm control relies on frequent deworming with benzimidazole                        unvaccinated and vaccinated, respectively. An efficacy of 50% implies
anthelminthics. As complementary approach for hookworm control,                         that vaccinated individuals have 50% fewer worms than unvaccinated
the HHVI is developing a first-generation recombinant vaccine with                      individuals. In addition to these parasitologic outcomes, the impact of
the goal to reduce hookworm disease burden. Methods: The                                the vaccine on clinical outcomes also requires evaluation. The
Ancylostoma Secreted Protein-2 (ASP-2), an abundant protein secreted                    morbidity from hookworm disease is directly related to intestinal blood
by infective hookworm larvae was selected on the basis of human                         loss caused by the adult hookworms. Diminished worm burden and
immunoepidemiological studies and results from laboratory animal                        fecal egg counts should be expected to result in reductions in host
vaccinations. Furthermore, it was shown that anti-ASP-2 inhibits                        intestinal blood loss, with the latter determined by quantitative fecal
hookworm larval invasion in vitro. A product development strategy to                    heme measurements. The primary sample size calculation had the
manufacture and test ASP-2 was generated in preparation for initial                     objective of detecting a vaccine efficacy of 30%; 1211 and 1730 eggs
safety studies in humans. Results: The antigen from Necator                             per gram in the unvaccinated and vaccinated arms, respectively. To
americanus, Na-ASP-2, was cloned and expressed in the yeast Pichia                      take account of the highly skewed distribution of the egg counts, this
pastoris. Process development, assay development and qualification,                     calculation used the negative binomial distribution, and yielded 505
cGMP pilot lot manufacture, toxicity and stability studies of the alum-                 people per arm, or 632 after allowing for losses to follow-up. Since
formulated Na-ASP-2 Hookworm Vaccine have been completed.                               fecal heme loss has been found to be approximately proportional to egg
Conclusions: Vaccination against hookworm would alleviate the public                    count, the above efficacy implies that mean fecal heme will also be
health deficiencies of drug treatment alone. After an initial Phase 1                   reduced by 30%. Fitting a gamma distribution to existing data from
study, the the clinical development of Na-ASP-2 Hookworm Vaccine                        the prospective field site, we estimated our power to detect such an
will include pilot efficacy studies in Brazil and Africa to evaluate                    effect to be 98%. Results: We have designed a double-blind,
clinical endpoints unique to helminth infections.                                       randomized placebo controlled Phase 2b proof of concept trial to
                                                                                        estimate of the efficacy of the Na-ASP-2 Hookworm Vaccine in
References:                                                                             reducing intensity of re-infection with hookworm in an adult
1. Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao S.                      hookworm infected populations from endemic areas of Brazil.
   Hookworm infection. N Eng J Med 2004; 351(8):799-807.                                Additional objectives are to investigate the effect of the vaccine on the
2. Hotez PJ, Zhan B, Bethony J, et al. Progress in the development of a                 clinical outcomes of hookworm disease by measuring using intestinal
   recombinant vaccine for human hookworm disease: the human                            blood loss (fecal heme). Conclusions: This vaccine brings to bear a
   hookworm vaccine initiative. Int J Parasitol 2003; 33(11):1245-                      number of innovative clinical trial design features. Including (a)
   1258.                                                                                measuring intensity of infection rather than incidence of disease; (b)
                                                                                        using a treatment and reinfection design to determine the efficacy of
                                                                                        the vaccine; (c) sampling across numerous geographic regions to avoid
                                                                                        interruption of transmission; (d) using fecal heme as a biomarker for
         The Human Hookworm Vaccine Initiative (HHVI): Novel Design                     the influence of hookworm infection on IDA; and (e) novel statistical
S8       and Statistical Considerations to Estimate the Efficacy of a
         Helminth Vaccine in Field Trials in Endemic Region: Phase 2b
                                                                                        approaches to deal with the over-dispersion of many of the parameters
                                                                                        of hookworm infection.
         Studies for a Human Hookworm Vaccine.
         J Bethony1, S Brooker 2, N Alexander2, S Geiger1, L Rodrigues 3,               References:
         ME Bottazzi1, K Stoever 3, P Hotez1                                            1. Brooker S, Bethony J, Rodrigues L, Alexander N, Geiger S, Hotez P.
         1
           The George Washington University, USA, 2 London School of Hygiene and           Epidemiologic, immunologic and practical considerations in
         Tropical Medicine, UK, 3 Sabin Vaccine Institute, USA                             developing and evaluating a human hookworm vaccine. Expert
                                                                                           Rev Vaccines 2005; 4(1):35-50.
    Background: An understanding of the epidemiology and                                2. Hotez PJ, Brooker S, Bethony JM, Bottazzi ME, Loukas A, Xiao
transmission dynamics of helminth infection is important for                               S. Hookworm infection. N Engl J Med 2004; 351(8):799-807.
determining the design, evaluation, and ultimate use of a hookworm
vaccine. Hookworms do not replicate within their hosts and, as such,
the traditional estimates of vaccine efficacy, which are based on the
comparison of incidence rates of infection and/or disease in vaccinated
and unvaccinated populations, are not appropriate. Furthermore, the


60
   on Vaccine Research
                                ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
          Safety and Immunogenicity of Vaccines against Cholera and                           sonnei in the framework of the vaccination program initiated in the
S9        Enterotoxigenic Escherichia coli Diarrhea in Children In Bangladesh-
          Problems Encountered and Milestones Achieved
                                                                                              Central, Volga, Northern Caucasus, Black Sea, Ural, and Yakutiya regions
                                                                                              of the Russian Federation. Chromatography-grade quality vaccine
          F. Qadri1, D. A. Sack2                                                              SHIGELLVAC was well tolerated by vaccinees in different age groups.
          1
            Laboratory Sciences Division, ICDDR,B, Dhaka, BANGLADESH, 2ICDDR,B,               Personal of food factories, food-handlers, and the staff of canteens and
          Dhaka, BANGLADESH.                                                                  cafés represented the immunized contingent. Among them special
                                                                                              attention was paid to immunization of the staff of milk factories and milk
    Background. In Bangladesh, the two major bacterial pathogens                              farms. Another aim of routine immunization was immunization of the
which contribute to the large burden of secretory diarrheal disease are                       staff of kindergartens and children’s summer camps, especially workers
Vibrio cholerae O1 and enterotoxigenic Escherichia coli (ETEC). Cholera                       connected with food processing. None of 60 food handlers immunized by
is more common in those more than two years of age and ETEC                                   SHIGELLVAC was infected during a large shigellosis outbreak in
infections in children less than three years of age. The vaccines tested at                   Krasnoturiinsk (mid-Ural area). Three months after vaccination,
the ICDDRB include killed and live oral vaccines for cholera and a killed                     immunized individuals demonstrated GM IHA titers of 1:1800, which
oral vaccine for ETEC. Methods. Oral vaccines were the whole cell                             was dramatically higher than titers observed after natural infection.
killed ETEC and cholera (SBL) as well as the live attenuated cholera
vaccine, Peru-15 (AVANT) which were tested in adults and children in                          Reference:
Bangladesh. Results. The ETEC vaccine was found to be safe and                                1. Aparin PG, Golovina ME, Ershov VI, Gancho TV, Shmigol VI,
immunogenic in adults and children up to 18 months of age (n=300).                               Pavlova LI, Chuprynina RP, Yolkina SI, Rachmanov RS, Lvov VL.
In infants, the full dose resulted in vomiting, requiring a reduction to a                       Systemic and mucosal (local) immune response after immunization
quarter dose. The reduced dose appeared safe and immunogenic (n=200)                             with new type low-endotoxic LPS Vaccine Shi
suggesting that this dose may be effective in primed populations. In
previous field studies the oral killed whole cell cholera vaccine proved

                                                                                              S11
efficacious, but protection waned more quickly in children, however                                     Randomized, Double-blind Phase I Study to Assess the Safety,
supplementation with zinc increased its immunogenicity (n=240). An                                      Tolerability, Imunogenicity, Dose Response, and Transmissibility of
alternative strategy is a single dose, live, vaccine candidate, Peru-15. This                           CVD 1208S, a guaBA, sen, and Set Deleted, Live, Oral Shigella
vaccine proved to be both safe and immunogenic in adults (n=70) and                                     flexneri 2a Soy Based Vaccine.
children (n=120). Conclusions. Oral vaccines for cholera and ETEC are                                   K. L. Kotloff1, J. K. Simon1, M. Pasetti1, J. P. Nataro1, M. B. Sztein1,
safe and immunogenic in adults in children in Bangladesh and further                                    S. S. Wasserman2, W. C. Blackwelder1, E. M. Barry2, M. M. Levine1
studies are needed to establishtheir efficacy, effectiveness and usefulness                             1
                                                                                                          Pediatrics, University of Maryland, Baltimore, MD, 2Medicine, University of
in this region.                                                                                         Maryland, Baltimore, MD.

References:                                                                                       Background: CVD1208S is a live, oral, S. flexneri 2a vaccine which
1. Firdausi Q, Tanvir A, Firoz A, et al. Safety and immunogenicity of an                      has been attenuated by deleting locus guaBA encoding two enzymes
   oral, inactivated enterotoxigenic Escherichia coli plus cholera toxin B                    integral to guanine nucleotide biosynthesis as well as set and sen, which
   subunit vaccine in Bangladeshi children 18-36 months of age.                               encode Shigella enterotoxin (ShET)1 and ShET2. CVD 1208S was
   Vaccine 2003; 21:2394-2403.                                                                constructed on animal-free media to address regulatory concerns about
2. Albert MJ, Qadri F, Wahed MA. et al. Supplementation with zinc,                            possible contamination with agents that cause Bovine Spongiform
   but not vitamin A, improves seroconversion to vibriocidal antibody                         Encephalopathy (BSE). Methods: Healthy inpatient adult volunteers
   in children given an oral cholera vaccine. J Infect Dis 2003; 187:909-                     were randomized in a double-blind fashion to receive one oral dose of
   913.                                                                                       CVD 1208S (108 or109 CFU, n=7 per dosage) or placebo (n=2).
                                                                                              Clinical, immunologic, and microbiologic responses were evaluated.
                                                                                              Results: One vaccine recipient (6%) experienced a brief (4 hour) episode
                                                                                              of low grade fever and another (6%) experienced mild diarrhea. Anti-LPS
                                                                                              responses as measured by antibody secreting cells, serum, or fecal
S10       Mass Vaccination Against Shigellosis: First Experience of Routine
          Immunization Against Shigella sonnei Infection
          R. P. Chuprinina1, L. I. Pavlova1, T. I. Frolushkina1, A. V. Protodiakonov1,
                                                                                              antibody, occurred in 57% of 108 CFU and 100% of 109 CFU
                                                                                              recipients. Over 86% of high dose vaccinees shed the vaccine strain for 2
          T. V. Gantcho2, M. E. Golovina2, V. I. Shmigol2, S. I. Elkina2, I. Y. Kurbatova2,   or more days. Transmission to placebo recipients was not detected.
          V. L. Lvov2, P. G. Aparin2                                                          Conclusions: CVD 1208S is well tolerated, immunogenic, easily
          1
            Carbohydrate Vaccines, Ministry of Health Russia, Moscow, RUSSIAN                 eradicated, and not transmitted to placebo recipients during a 10 day
          FEDERATION, 2Carbohydrate Vaccines, NRC-Institute of Immunology, Moscow,            inpatient stay. CVD1208S is a promising Shigella vaccine candidate
          RUSSIAN FEDERATION.                                                                 suitable for outpatient phase II testing.

    Newly-developed low-endotoxic lipopolysaccharide Shigella sonnei                          References:
vaccine SHIGELLVAC protected civic population from natural infection                          1. Kotloff, KL, Pasetti MF, Barry EM, et al. Deletion in the Shigella
in endemic region with efficacy rate higher than 90% (phase III clinical                         enterotoxin genes further attenuates Shigella flexneri 2a bearing
trials). The vaccine was officially approved for routine immunization of                         guanine auxotrophy in a phase 2 trial of CVD 1204 and CVD 1208.
children older than 3 years old and adults by MOH Russia in September                            J Infect Dis 2004; 190(10):1745-1754.
2003. The strategy of routine immunization against food-borne                                 2. Kotloff KL, Noriega FR, Taraz Samandari T, et al. Shigella flexneri 2a
shigellosis was formulated based on the vaccine characteristics and                              strain CVD 1207, with specific deletions in virG, sen, set, and guaBA,
epidemiological background of disease distribution. Approximately                                is highly attenuated in humans. Infect Immun 2000; 68(3):1034-
100,000 persons from 3 to 70 years were single immunized with Shigella                           1039.                                                        (continued)


                                                                                                                                                                                  61
        Eighth Annual Conference
                               ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
          Phase 1 Study of the Safety and Immunogenicity of Amai-                         administered to 87%, overall. The rate of ORS was 18/320 (5.6%;
S12       C1/Alhydrogel® Vaccine for Plasmodium falciparum Malaria in
          Semi-Immune Malian Adults
                                                                                          95%CI 3.6%-8.7%) and 3/370 (0.8%; 95%CI 0.3%-2.4%) in QC and
                                                                                          BC, respectively. 95% of parents would immunize their child again if
          A. Dicko1, D. Diemert2, I. Sagara1, M. Sogoba1, M. Niambele1, M. Assadou1,      the vaccine was free. Other AEFIs occurring within 72 hrs of
          O. Guindo1, B. Kamate1, M. Baby1, M. Sissoko1, G. Mullen2, E. Malkin2,          vaccination included fussiness (19%; 95%CI 16-22%), fever (11%;
          M. Sissoko1, M. Thera1, A. Dolo1, C. Long2, D. Diallo1, L. Miller2, A. Saul2,   95%CI 9-14%), drowsiness (7%; 95%CI 5-9%) and vomiting (2%;
          O. Doumbo1                                                                      95%CI 1-4%). Conclusions: Influenza vaccine was well-tolerated. The
          1
            MRTC/University of Bamako, Bamako, MALI, 2MVDB/NIAID, Rockville, MD.          frequency of ORS was low and consistent with the background rate of
                                                                                          acute respiratory illness in this agegroup[2]. Differences in rates of
    Apical membrane antigen-1 (AMA1) - a leading malaria vaccine                          ORS between QC/BC may relate to interview approach or distribution
candidate - is a surface protein expressed during the asexual blood stage                 of background confounders (infection/allergy/asthma).
of P. falciparum that has been implicated in parasite invasion of
erythrocytes. AMA1-C1/Alhydrogel® consists of an equal mixture of                         References:
AMA1 from the FVO and 3D7 clones of P. falciparum, produced                               1. Skowronski DM, Bjornson G, Husain E, Metzger DL, Scheifele
separately as recombinant proteins expressed by Pichia pastoris, then                        DW. Oculorespiratory syndrome after influenza immunization in
mixed and adsorbed onto Alhydrogel®. In a double-blinded Phase 1                             children. Pediatr Infect Dis J. 2005; 24:63-69.
study, 54 healthy Malian adults were enrolled into one of three dose                      2. Monto AS, Ullman BM. Acute respiratory illness in an American
cohorts (n=18 per cohort) and randomized 2:1 to receive either AMA1-                         community : the Tecumseh study. JAMA 1974;227:165-169.
C1/Alhydrogel® or Recombivax® hepatitis B vaccine. The first,
second and third cohorts were vaccinated successively at three-week
intervals, and received 5, 20 and 80 mcg of AMA1-C1, respectively. 53
                                                                                                    Improved Protective Antibody Responses Were Induced by Codon
                                                                                          S14
subjects received both of 2 scheduled immunizations on Days 0 and 28,
and all cohorts have completed 180 days of follow-up. No vaccine-                                   Optimized DNA Vaccines Expressing Hemagglutinin Antigens of
related serious or grade 3 adverse events have been observed. All                                   Influenza H1 and H3 Serotypes
injection site reactions were mild in severity, whereas systemic reactions                          S. Wang1, I. Mboujka1, J. Haran1, H. Cao1, X. Huang1, J. Taaffe2, A. Solórzano2,
were mild to moderate in severity. Anti-AMA1 antibody responses are                                 A. García-Sastre2, S. Lu1
being measured by ELISA on sera collected at pre- and post-vaccination                              1
                                                                                                      Department of Medicine, University of Massachusetts Medical School,
time-points. The data so far demonstrate that AMA1-C1/Alhydrogel®                                   Worcester, MA, 2Department of Microbiology, Mount Sinai School of Medicine,
has an excellent safety profile. Full safety and immunogenicity results                             New York, NY.
will be reported.
                                                                                              Background: Influenza viral infection (flu) remains an important
Reference:                                                                                public health issue. Alternative vaccination strategies are needed to
1. Stowers AW, Kennedy MC, Keegan BP, Saul A, Long CA, Miller LH.                         improve the quality of immune responses and to overcome the
   Vaccination of monkeys with recombinant Plasmodium falciparum                          limitation of the manufacturing process for the current inactivated flu
   apical membrane antigen 1 confers protection against blood-stage                       vaccines. Early generations of flu DNA vaccine, while protective in
   malaria. Infect Immun 2002; 70(12):6961-6967.                                          small animal models, could not elicit detectable antibody responses
                                                                                          prior to viral challenge. We have developed codon optimized Flu HA
                                                                                          genes to improve the immunogenicity of Flu DNA vaccines. Methods:
                                                                                          Codon optimized HA inserts for A/H1N1/NewCal/20/99 (H1) and
                                                                                          A/H3N2/Panama/2007/99 (H3) were produced and individually
S13       Oculo-respiratory Syndrome (ORS) and Other Adverse Events
          Following Immunization (AEFIs) in Infants and Toddlers Given
          Influenza Vaccine
                                                                                          subcloned into DNA vaccine vector pSW3891. The HA gene inserts
                                                                                          were designed to express either cell associated or secreted forms of HA
                                                                                          antigens. New Zealand White rabbits received 4 bi-weekly gene gun
          D. M. Skowronski1, S. A. Tweed1, V. Remple1, K. Pielak1, J. Daigneault2,
                                                                                          immunizations. Rabbit sera were collected for antibody analyses.
          P. Daly3, G. Arsenault4, E. Galanis1, T. Tam5
                                                                                          Results: Codon optimized HA DNA vaccines elicited significant levels
          1
            BC Centre for Disease Control, Vancouver, BC, CANADA, 2Direction de Sante
                                                                                          of anti-HA IgG responses with strong serotype specificity as
          Publique, Chicoutimi, PQ, CANADA, 3Vancouver Coastal Health Authority,
                                                                                          determined by ELISA and Western blot. Co-delivery of HA DNA
          Vancouver, BC, CANADA, 4Fraser Health Authority, Surrey, BC, CANADA, 5Public
                                                                                          vaccines from two serotypes expanded the breadth of anti-HA IgG
          Health Agency of Canada, Ottawa, ON, CANADA.
                                                                                          responses to include both serotypes. Significant levels of HI activities
                                                                                          were also observed with codon optimized HA DNA vaccines.
    Background: ORS following influenza vaccine (FV) was first
                                                                                          Conclusions: Codon optimization was able to improve the
reported in Canada in 2000-2001. The rate of ORS in children in 2000
                                                                                          immunogenicity of influenza DNA vaccines and it offers an alternative
(10-15%) was highest among first-time vaccinees (24%)[1]. In 2004-
                                                                                          vaccination strategy to the current flu vaccines.
2005, expert groups recommended influenza vaccination for children
aged 6-23 mos for the first time. We assessed ORS and other AEFIs
                                                                                          Reference:
among infants/toddlers receiving FV in Quebec (QC) and British
                                                                                          1. Palese P, Garcia-Sastre A. Influenza vaccines: present and future. J
Columbia (BC), Canada in fall, 2004. Methods: Study consent was
                                                                                             Clin Invest 2002; 110:9-13.
obtained from parents bringing their infant/toddler to public clinics for
influenza immunization. Telephone interviews were conducted 6-10
days later using a standard questionnaire. Results: 320 children in QC
and 370 in BC participated; first-time vaccinees accounted for 307
(96%) and 291 (79%), respectively. The same lot number was

62
   on Vaccine Research
                              ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
         Protective Measures and Human Antibody Response to HPAI                         that epitopes were processed and presented to the immune system
S15      H7N3 in British Columbia (BC), Canada
         D. M. Skowronski1, Y. Li2, S. A. Tweed1, T. Tam3, M. Petric1, S. Berger1,
                                                                                         during natural infection was tested using in vitro recall responses as
                                                                                         measured using PBMC from normal donors, peptide pools and
         A. Larder4, N. Bastien2, A. King3, R.C. Brunham1                                ELISPOT IFN-_ assays. In our initial studies, 19 of 39 HLA-A2-
         1
           BC Centre for Disease Control, Vancouver, BC, CANADA, 2Public Health Agency   restricted peptides induced measurable responses in the range of 10-
         of Canada, Winnipeg, MB, CANADA, 3Public Health Agency of Canada, Ottawa,       6,000 spot forming cells/106 PBMC. These preliminary data
         ON, CANADA, 4Fraser Health, Abbotsford, BC, CANADA.                             demonstrate that virally conserved CTL epitopes can be identified and
                                                                                         support our belief that a vaccine designed for use in a “first response”
    Background: In spring,2003 a poultry outbreak of highly-                             mode during the early stage of a pandemic is feasible.
pathogenic-avian-influenza (HPAI)-H7N7 in the Netherlands caused
89 human infections. Modified hemagglutination inhibition (HI) assay                     References:
detected antibody in >50% of 500 potentially-exposed persons[1]. In                      1. Seo SH, Peiris M, Webster RG. Protective cross-reactive cellular
spring,2004 an HPAI-H7N3 poultry outbreak in BC, Canada caused                              immunity to lethal A/Goose/Guangdong/1/96-like H5N1 influenza
two human infections. We report compliance with protective measures                         virus is correlated with the proportion of pulmonary CD8+ T cells
and sero-survey for additional cases in BC. Methods: All sera from                          expressing gamma interferon. J Virol 2002; 76:4886-4890.
volunteers among those potentially exposed to AI-infected                                2. Webby RJ, Andreansky S, Stambas J, Rehg JE, Webster RG, Doherty
poultry/products in BC were tested by microneutralization (MN) assay.                       PC. Protection and compensation in the influenza virus-specific
Sera from two confirmed human infections, a random sample of ten                            CD8+ T cell response. Proc Natl Acad Sci U S A
participants and four persons with unprotected exposure to AI-infected                               2003;100:7235-7240.
birds were also tested by Western blot, routine and modified HI (using
horse erythrocytes)[2]. Results: 167 persons participated between May
7 and July 26, 2004. Of 91 persons who handled or shared confined
                                                                                                   Immunization with Salmonella enterica serovar Typhi Ty21a
airspace with AI-infected poultry, 21 (23%) experienced
conjunctivitis/influenza-like illness. Among 65 persons present in barns
with AI-infected birds and sawdust, 85% received influenza vaccine,
                                                                                         S17       Expressing Anthrax Protective Antigen Protects Mice from an
                                                                                                   Anthrax Lethal Toxin Challenge
74% took oseltamavir and 85%, 83% and 55% always wore gloves,                                      Y. Wu, M. Osorio, S. Bhattacharyya, M. D. Bray, R. Walker, D. J. Kopecko
mask or goggles, respectively. All assays were negative for antibody to                            FDA-CBER, Bethesda, MD.
H7. Conclusions: Improved compliance with protective measures,
especially goggles, is needed during poultry outbreaks. Possible reasons                     The current FDA-approved anthrax vaccine is an aluminum
for fewer infections compared to the Netherlands include: lower                          hydroxide-adsorbed, formalin-treated culture supernatant of toxigenic,
pathogenicity of H7N3, better compliance with protective measures                        nonecapsulated strain of B. anthracis. The principal protective
and/or sampling/testing considerations.                                                  component of this vaccine is the protective antigen (PA) protein.
                                                                                         Although the vaccine is safe and efficacious, it does have some
References:                                                                              limitations such as a high index of local and systemic reactions, it is
1. Bosman A, Mulder YM, de Leeuw JRJ, et al. Executive summary                           administered subcutaneously, and requires multiple doses to stimulate
   avian flu epidemic 2003: public health consequences. RIVM rapport                     immunity. In an attempt to design an improved anthrax vaccine for easy
   630940003. Bilthoven:RIVM; 2004.                                                      emergency immunization, we have chosen to test the feasibility of using
   http://www.rivm.nl/bibliotheek/rapporte                                               an attenuated Salmonella serovar typhi strain (Ty21a) expressing PA to
2. Stephenson I, Wood JM, Nicholson KG, Zambon MC. Sialic acid                           induce an immune response to PA and thus protect against anthrax
   receptor specificity on erythrocytes affects detection of antibody to                 infection. In these studies, the anthrax PA was cloned behind an
   avian influenza hemagglutinin. J Med Virol 2003; 70:391-398.                          environmentally regulated promoter in a genetically stable low copy
                                                                                         plasmid vector, pGB-2. Preliminary mouse studies showed that the live
                                                                                         vector expressing PA elicited a robust immune response measured by
                                                                                         PA-specific IgG ELISA titers. Antibody titers were significantly
                                                                                         increased when the live vector expressed an extracellularly secreted form
S16      T Cell Multi-Epitope Vaccine for Pandemic Influenza
         J. Alexander1, B. Stewart1, P. Bilsel1, J. Katz2, M. Newman1
         1
           Epimmune, San Diego, CA, 2Centers for Disease Control and Prevention,
                                                                                         of PA. A challenge of immunized mice with approximately 5 LD50
                                                                                         doses of anthrax lethal toxin (given i.v.) showed that vaccine constructs
                                                                                         induced protective immunity in 75 % of vaccinated animals. Ty21a has
         Atlanta, GA.
                                                                                         been administered to greater than 25 million people and proven to be
                                                                                         safe. Thus, a live attenuated oral vaccine such as Ty21a expressing PA
    The goal of our project is to develop vaccines for use against
                                                                                         could form the basis of a safe and effective vaccine against anthrax
pandemic strains of influenza virus. Vaccine design was based on use of
multiple sequence conserved T cell (CTL and HTL) epitopes. Vaccines
                                                                                         References:
that induce T-cell responses can be designed and produced
                                                                                         1. Pitt ML, Little S, Ivins BE, Fellows P, Boles J, Barth J, Hewetson J,
prospectively and used early in a pandemic, prior to availability of
                                                                                            Friedlander AM. In vitro correlate of immunity in an animal model of
strain-matched vaccines which induce antibody responses. Epitopes
                                                                                            inhalational anthrax. J Appl Microbiol 1999; 87(2): 304.
were identified using sequences of influenza virus strains which are
                                                                                         2. Xu DQ, Cisar JO, Ambulos Jr N Jr, Burr DH, Kopecko DJ.
potential components of a pandemic influenza virus including agents of
                                                                                            Molecular cloning and characterization of genes for Shigella sonnei
past pandemics and zoonotic influenza infections of man. An effective
                                                                                            form I O polysaccharide: proposed biosynthetic pathway and stable
process based on motif search algorithms and HLA-peptide binding
                                                                                            expression in a live salmonella vaccine vector. Infect Immun 2002;
assays was employed to identify epitopes that are restricted by multiple
                                                                                            70(8):4414-4423.
HLA types and with predictable immunogenicity levels. Confirmation                                                                                       (continued)


                                                                                                                                                                              63
        Eighth Annual Conference
                                ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
          Assessment of the Reactogenicity of Tdap in Children and                           pAT153/Cfrag was the most stable plasmid in vitro and in vivo.
S18       Adolescents 7-19 Years of Age by Interval Since Prior Tetanus and
          Diphtheria Toxoids Containing Vaccine
                                                                                             Although all plasmids elicited similar antibody responses to Salmonella
                                                                                             LPS, only pAT153/Cfrag induced a Cfrag antibody response. At day 28
          S. A. Halperin1, L. Sweet2, D. Baxendale1, A. Neatby2, P. Rykers1, B. Smith1,      all SPI mutants were able to colonise, however, _aroAD(ssrA) was
          M. Zelman2, D. Maus3, P. Lavigne3, M. Decker3                                      significantly reduced in the Peyer’s patches compared with _aroAD
          1
            Dalhousie University, Halifax, NS, CANADA, 2Department of Health and Social      (p=0.03). Only 2/5 (day 28) and 1/5 (day 56) mice immunised with
          Services, Charlottetown, PE, CANADA, 3Sanofi Pasteur, Toronto ON, CANADA,          _aroAD(ssrA) produced a Cfrag antibody response. At day 56 _aroAD
          and Swiftwater, PA, USA                                                            had significantly higher Ig and IgG1 Cfrag titres than all SPI mutants
                                                                                             (p<0.03).
    Background: The incidence of pertussis is increasing amongst                             Conclusion: Our research shows attenuated Salmonella enterica can be
adolescents and adults, despite widespread immunization prior to                             used to orally deliver vaccine antigens. However, consideration must be
school entry. Adult-formulation diphtheria and tetanus toxoids and                           given to the plasmid vector and strain of Salmonella used as these impact
acellular pertussis vaccines (Tdap) have been developed to prevent                           on the response to the vaccine.
pertussis in adolescents and adults. Methods: To evaluate whether
recent receipt of diphtheria-tetanus-toxoid-containing-vaccine                               Reference:
(TD/Td) might contraindicate receipt of Tdap, we performed an open-                          1. Dunstan, SJ, Simmons CP, Strugnell RA. In vitro and in vivo stability
label, province-wide, clinical trial comparing the reactogenicity of Tdap                       of recombinant plasmids in a vaccine strain of Salmonella enterica var.
(Adacel‘, Sanofi-Pasteur) given 2-9 years versus ≥10 years after previous                       Typhimurium. FEMS Immunol Med Microbiol 2003; 37(2-3):111-
TD/Td. Results: 7001 children/adolescents were enrolled in the study                            119.
(464-963/interval cohort); adverse event diaries were completed by
5926 (85%). No Arthus reactions or serious adverse events related to
vaccination were reported. No differences in reports of fever were
found by interval since last immunization. Injection-site erythema and
swelling were modestly increased among those with most recent prior
TD/Td. Compared to the 10-year-interval group, the maximum
                                                                                             S20      CpG Oligodeoxynucleotides Co-administered With the Microneme
                                                                                                      Protein MIC2 Protect Against Eimeria Infections
                                                                                                      R. A. Dalloul1, H. S. Lillehoj1, D. M. Klinman2, X. Ding1, W. Min1,
increase for any other group was £8.4% for any erythema, £6% for                                      R. A. Heckert1, E. P. Lillehoj3
moderate/severe erythema, £10.2% for any swelling, £6.9% for                                          1
                                                                                                        Animal Parasitic Diseases Laboratory, USDA, Beltsville, MD, 2Section of
moderate/severe swelling, £5.1% for any pain, and £3.5% for                                           Retroviral Immunology, Center for Biologics Evaluation & Research, US FDA,
moderate/severe pain. Conclusion: Although there is a modest increase                                 Bethesda, MD, 3Department of Pediatrics, School of Medicine, University of
in injection-site events with decreasing interval since a previous                                    Maryland, Baltimore, MD.
immunization, Adacel™ (Tdap) can be safely administered at intervals
of ≥2 years since a previous TD/Td vaccine.                                                      Short synthetic oligodeoxynucleotides containing unmethylated
                                                                                             CpG motifs (CpG ODNs) were previously shown to exert a positive
References:                                                                                  effect on weight loss and oocyst shedding associated with Eimeria
1. National Advisory Committee on Immunization. Prevention of                                infection when injected in vivo. The present work investigated the
   pertussis in adolescents and adults. Can Commun Dis Rep 2003;                             effects of in ovo vaccination with CpG ODNs and an Eimeria
   28:ACS-5,6.                                                                               recombinant microneme protein (MIC2), alone or in combination, on
2. Rennels MB, Deloira MA, Pichichero ME, et al. Extensive swelling                          chicken susceptibility to coccidiosis. In ovo injection of CpG ODNs
   after booster doses of acellular pertussis-tetanus-diphtheria vaccines.                   alone enhanced resistance to experimental E. acervulina infection as best
   Pediatrics 2000; 105(1):e12.                                                              exemplified by reduced oocyst shedding. Two CpG ODNs reduced the
                                                                                             oocyst load, but did not affect weight gain. When co-administered with
                                                                                             the recombinant microneme protein, both ODNs reduced oocyst
                                                                                             shedding; however, only ODN D19 plus MIC2 consistently improved
                                                                                             weight gain. Vaccinating with ODN 2006 or MIC2 protein curtailed
S19       Oral Vaccine Delivery by Salmonella Vaccine Vectors
          M. E. Gahan1, D. E. Webster2, S. L. Wesselingh2, B. B. Finlay3, R. A. Strugnell4
          1
            Macfarlane Burnet Institute & Department of Medicine, Monash University,
                                                                                             oocyst shedding but did not enhance weight gain in E. tenella-infected
                                                                                             birds. Co-administration of CpG ODN and MIC2 did not have an
                                                                                             additive effect in reducing the oocyst output; however, it resulted in the
          Melbourne, AUSTRALIA, 2Macfarlane Burnet Institute, Melbourne, AUSTRALIA,
                                                                                             highest and lowest Ab response before and after E. tenella infection,
          3
            Michael Smith Laboratories, University of British Columbia, Vancouver, BC,
                                                                                             respectively. Collectively, CpG ODNs administered in ovo
          CANADA, 4Department of Microbiology and Immunology, University of
                                                                                             demonstrated immunoenhancing and adjuvant effects following Eimeria
          Melbourne, Melbourne, AUSTRALIA.
                                                                                             infections.
    Background: Salmonella enterica is an ideal candidate for oral
                                                                                             References:
delivery of vaccine antigens. We report on the effects of plasmid vector
                                                                                             1. Dalloul RA, Lillehoj HS, Klinman DM, et al. In ovo administration
and Salmonella strain on the immune response to the C-fragment of
                                                                                                of CpG oligodeoxynucleotides and the recombinant microneme
tetanus toxin (Cfrag). Methods: Cfrag (+pCMV) was ligated into the
                                                                                                protein MIC2 protects against Eimeria infections. Vaccine 2005; in
plasmids pcDNA3, pAT153, pBBR122, pBR322, pRSF1010, pUC18
                                                                                                press.
and pACYC184 and transformed into _aroAD Salmonella. In vitro and
                                                                                             2. Klinman DM. Immunotherapeutic uses of CpG
in vivo plasmid stability was examined and correlated with Cfrag
                                                                                                oligodeoxynucleotides. Nat Rev Immunol 2004; 4:249-259.
antibody response. Additional Salmonella Pathogenicity Island (SPI)
mutations (ssrA, invA and sifA) were transduced into _aroAD. Organ
counts and Cfrag antibody titres were determined. Results:

64
  on Vaccine Research
                              ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
         Immunogenicity of Combination DNA Vaccines for RVFV, TBEV,                       measles-specific SI. Of all haplotypes analyzed, A*02-Cw*07-B*07
S21      HTNV, and CCHFV
         K.W. Spik, A. Shurtleff, A.K. McElroy, M.C. Guttieri, J. W. Hooper, and C.
                                                                                          (p=.03), A*01-Cw*07-B*08 (p=.02), DPB*04-DQB*02-DRB*03
                                                                                          (p=.006) were associated with lower cellular responses to mumps.
         Schmaljohn                                                                       Interestingly, A*26-Cw*12-B*38 (p=.01) and DPB*04-DQB*05-
         Virology Division, United States Army Medical Research Institute of Infectious   DRB*01 (p=.008) were associated with high SI. Specific haplotypes
         Diseases, Fort Detrick, Frederick, MD 21702                                      associated with both rubella high and low SI were DPB*03-DQB*06-
                                                                                          DRB*06 (p<.001) and DPB*11-DQB*02-DRB*07 (p=.003),
    Background: Rift Valley fever virus (RVFV), Crimean Congo                             respectively. Conclusion: These data further confirm that humoral and
hemorrhagic fever virus (CCHFV), Hantaan virus (HTNV), and tick-                          cellular responses to MMR vaccine are genetically restricted by HLA
borne encephalitis virus (TBEV) cause serious infections in humans.                       genes.
Licensed vaccines against these pathogens are not currently available.
Methods: We constructed DNA vaccines for RVFV and CCHFV by                                Reference:
cloning cDNA representing M segment coding regions into a plasmid                         1. Ovsyannikova IG, Jacobson RM, Vierkant RA, Jacobsen SJ, Pankratz
with a CMV promoter. We vaccinated mice by gene gun with these                               VS, Poland GA. Human leukocyte antigen class II alleles and rubella-
vaccines alone or combined with previously developed DNA vaccines                            specific humoral and cell-mediated immunity following measles-
for TBEV (1) and HTNV (2). We measured antibody responses by                                 mumps-rubella-II vaccination. J Infect Dis 2005; 191:515-519.
immune precipitation of proteins and by neutralization assays. Results:
The TBEV vaccine and a RVFV vaccine encoding the envelope
glycoproteins elicited neutralizing antibodies and afforded protective
immunity when delivered alone or combined with other DNA vaccines.
Although low levels of antibodies were elicited with the HTNV or
                                                                                          S23      Correlations among Measles Virus-Specific Antibody,
                                                                                                   Lymphoproliferation and Th1/Th2 Cytokine Responses Following
                                                                                                   MMR-II Vaccination
CCHFV vaccines, no major differences were observed when they were
                                                                                                   N. Dhiman, I. G. Ovsyannikova, J. E. Ryan, R. M. Jacobson, R. A. Vierkant,
delivered alone or combined with other DNA vaccines. Conclusions:
                                                                                                   S. V. Pankratz, S. J. Jacobsen, G. A. Poland
These data suggest that combination DNA vaccines for these agents are
                                                                                                   Mayo Vaccine Research Group, Mayo Clinic College of Medicine, Rochester, MN.
possible, but further studies in other animal models and with other
delivery methods are desirable.
                                                                                              Introduction: Measles immunity is conferred by humoral and
                                                                                          cellular immune responses, later being critical in long-term protection
References:
                                                                                          against measles infection. Methods: We examined measles-specific
1. Schmaljohn C, Custer D, VanderZanden L, Spik K, Rossi C, Bray
                                                                                          antibodies, lymphoproliferation and Th1/Th2 signature cytokines, IFN-
   M. Evaluation of tick-borne encephalitis DNA vaccines in monkeys.
                                                                                          _ and IL-4, in population-based cohort of healthy children from
   Virology 1999; 263:166-174.
                                                                                          Olmsted County, Minnesota after measles-mumps-rubella-II (MMR-II)
2. Hooper, JW, Custer DM, Thompson E, Schmaljohn CS. DNA
                                                                                          two-dose vaccination. Results: We detected positive measles-specific
   vaccination with the Hantaan virus M gene protects hamsters against
                                                                                          cellular and humoral immunity in majority of our study population.
   three of four HFRS hantaviruses and elicits a high-titer neutralizing
                                                                                          However, a small proportion of subjects demonstrated an immune
   antibody response in Rhesus monkeys. J Virol 2001; 75:8469-8477.
                                                                                          response skewed towards the Th2 type, characterized by the presence of
                                                                                          either IL-4 and/or measles-specific antibodies and a lack of positive
                                                                                          lymphoproliferation and IFN-_ production. Further, we observed
                                                                                          significant positive correlation between lymphoproliferation and
S22      Genetic Influence of HLA Haplotypes on Immune Responses
         Following Measles-Mumps-Rubella (MMR-II) Vaccination
         in Children
                                                                                          secretion of IFN-_ (r= 0.20, p=0.0002) and IL-4 (r=0.15, p=0.005).
                                                                                          Measles antibody levels were associated with lymphoproliferation
                                                                                          (r=0.12, p=0.03), but lacked correlation to either cytokine type.
         I. G. Ovsyannikova1, S. V. Pankratz2, R. M. Jacobson1, R. A. Vierkant2,
                                                                                          Conclusions: We demonstrated both cellular and humoral responses
         G. A. Poland1
                                                                                          after the recommended MMR-II vaccination in a significant proportion
         1
           Vaccine Research Group, Mayo Clinic College of Medicine, Rochester, MN,
                                                                                          of study subjects. Further, a positive correlation between
         2
           Health Science Research, Mayo Clinic College of Medicine, Rochester, MN.
                                                                                          lymphoproliferation and IL-4 and IFN-_ suggests that immunity to
                                                                                          measles may be maintained by both the Th1 and Th2 cells. On the other
    Background: The variability of humoral (antibody, Ab) and cellular
                                                                                          hand, biased humoral response observed in a subset of subjects may be
(lymphocyte proliferation) immune responses modulated by HLA
                                                                                          insufficient to provide long-term immunity. Lack of correlation between
genes is a significant factor in the protective effect of the MMR
                                                                                          antibody levels and Th1/Th2 cytokines may explain skewed immune
vaccine. Methods: We studied the association between measures of
                                                                                          responses in these individuals. Further work on the determinants of
immune responses and HLA alleles among 346 children who previously
                                                                                          Th1/Th2 skewing of the immune response is needed.
received two doses of the MMR vaccine. Haplotype effects were
estimated using an approach that accounts for linkage phase ambiguity
                                                                                          References:
via an Expectation Maximization algorithm. Results: Mean values for
                                                                                          1. Dhiman N, Ovsyannikova IG, Jacobson RM, et al. Correlates of
measles, mumps and rubella Abs and stimulation indices (SI) were
                                                                                             lymphoproliferative responses to measles, mumps, and rubella
2040, 1034, 50 IU/ml and 5.1, 7.3, 3.3, respectively. Specifically,
                                                                                             (MMR) virus vaccines following MMR-II vaccination in healthy
DPB*04-DQB*03-DRB*07 (p=.001) and DPB*04-DQB*06-DRB*02
                                                                                             children. Clin Immunol 2005; in press.
(p=.02) haplotypes were associated with lower levels of measles-induced
                                                                                          2. Ovsyannikova IG, Jacobson RM, Ryan JE, et al. HLA class II alleles
Abs. In contrast, DPB*03-DQB*03-DRB*04 (p=.02) was positively
                                                                                             and measles virus-specific cytokine immune response following two
associated with lymphoproliferation to measles antigens, whereas
                                                                                             doses of measles vaccine. Immunogenetics 2005; 56:798-807.
DPB*04-DQB*02-DRB*03 (p=.01) was negatively associated with                                                                                           (continued)


                                                                                                                                                                           65
        Eighth Annual Conference
                           ABSTRACTS OF ORAL SUBMITTED PRESENTATIONS
         Mumps Virus Vaccine Strain Urabe AM9: Identification of
S24      Nucleotide Changes Asociated with Variability in the
         Neurovirulent Phenotype
         C. J. Sauder, S. A. Rubin, K. M. Vandenburgh, K. M. Carbone
         FDA/CBER, Bethesda, MD.

    Mumps virus is a highly neurotropic virus. We previously described
a rat model for prediction of mumps virus neurovirulence in humans.
The degree of hydrocephalus in brains of rats following neonatal
infection with different mumps virus strains correlated with the strain’s
apparent neurovirulent potential in humans. The Urabe AM9 vaccine
strain, which causes meningitis in about 1 in 10,000 vaccinees,
exhibited considerable neurovirulence in this rat model. In order to
identify the genetic basis of Urabe AM9 neurovirulence, we sought to
alter the virus phenotype by repeated passaging in various cell lines.
Employing our neonatal rat model, we found that the in vitro passaged
virus exhibited various degrees of attenuation. Attenuation was found
to be most pronounced in Urabe AM9 passaged six times in chicken
embryo fibroblasts (CEF) and human 293 cells. The nucleotide
sequence of parental Urabe AM9 as well as of the virus passaged in CEF
cells was determined. Attenuation was associated both with a
disappearance and evolution of nucleotide heterogeneity on 20
positions, 13 of which involving amino acid changes. Using this
knowledge, the relevance for neurovirulence of individual mutations
can be analysed in future studies employing mumps virus reverse
genetics technology.

References:
1. Rubin SA, Pletnikov M, Taffs R, et al. Evaluation of a neonatal rat
   model for prediction of mumps virus neurovirulence in humans. J.
   Virol. 2000; 74:5382-5384.
2. Amexis G, Fineschi N, Chumakov K. Correlation of genetic
   variability with safety of mumps vaccine Urabe AM9 strain. Virology
   2001; 287:234-241.




66
on Vaccine Research




  ABSTRACTS OF
SUBMITTED POSTER
 PRESENTATIONS




                      67
        Eighth Annual Conference
                               ABSTRACTS OF INVITED PRESENTATIONS
                           ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
          Immune Responses Induced by Intranasal Immunization with                  Methods: Female mice were immunized intratracheally (i.t.) or
P1        Influenza H3N2-anti-H3N2
          Complex in Mice
                                                                                    intranasally (i.n.) with recombinant, endotoxin-depleted F1 antigen and
                                                                                    flagellin or a mutant flagellin and boosted at 4 weeks. Plasma antibody
          X. Yao, Y. Wen                                                            titers to F1 antigen were determined by ELISA. Immunized and control
          Fudan University, Shanghai, CHINA.                                        mice were challenged i.n. with 1.2x105 cfu Y. pestis CO92, a dose
                                                                                    equivalent to 100 times the LD50. Statistical significance and LD50
    Intranasal delivery of inactivated influenza virus in mice can provide          values were determined using SigmaStat3.1. Results: Flagellin-treated
protection against the homologous virus as well as heterologous strains             mice had a dramatic increase in anti-F1 plasma IgG titers that remained
due to the high cross-reactivity of IgA antibody in mucosal secretions.             stable over time. Using C3H/HeN and C3H/HeJ mice, we found that
Our previous study showed that Hepatitis B Surface Antigen/Antibodies               signaling via TLR5/4 heteromeric complexes was not required for the
complexes can induce strong humoral immune responses when delivered                 adjuvant effect of flagellin. Type I and II interferons, TNF-_, and IL-6
by a mucosal route. In this study, 15_g H3N2 antigen complexed with                 are also not essential for adjuvant activity. Finally, immunization with
mouse antibodies against H3N2 (anti-H3N2) was administered to                       flagellin and the F1 antigen was protective for i.n. challenge with
BALB/c mice by intranasal inhalation. Mice were divided into 5 groups               virulent Y. pestis CO92. Conclusion: Mucosal immunization with
(8 mice per group), namely, intranasal immunization with only H3N2,                 recombinant F1 antigen and flagellin promotes a strong humoral
H3N2+CpG, H3N2+Polyethylene glycol, H3N2+anti-H3N2 and the                          response that is protective against intranasal challenge with Y. pestis.
controls. Each group of mice was immunized with H3N2 15_g with
different adjuvants for three times of immunization at three-week                   Reference:
intervals. Compared to mice immunized with H3N2 alone, mice                         1. Honko AN, Mizel SB. Mucosal administration of flagellin induces
immunized with antigen-antibody complex showed significant increase                    innate immunity in the mouse lung. Infect Immun 2004; 72:6676-
in mucosal IgA (Geometric mean: H3N2 16.82, H3N2+anti-H3N2                             6679.
113.14, H3N2+CpG 226.27, H3N2 Vs H3N2+anti-H3N2) (P< 0.01)
H3N2+anti-H3N2 Vs H3N2+CpG (P>0.05). The statistical
                                                                                             Induction of Active Immune Suppression by Co-immunization
significance of the difference between groups was calculated by Student’s
two-tailed t test using the Excel program(Microsoft). Serum                         P3       of DNA-protein Vvaccines
                                                                                             B. Wang, H. Jin, Y. Kang
immunoglobulin G (IgG) antibodies specific to Influenza virus was also
detected in all study groups. By ELISA, anti-H3N2 titer ranged from                          State Key Lab for Agro-Biotechnology, China Agricultural University,
51,200 to 819,200; the highest being H3N2+CPG group, and the                                 Beijing, CHINA.
second high was the H3N2 antigen-antibody group, the lowest was
                                                                                        Background: Induction of immune tolerance via protein-based
H3N2 group. These results indicate that intranasal immunization using
                                                                                    vaccines has been exploited for treating autoimmune disease such as
hemagglutinin antigen- antibody complex, or antigen with CpG can
                                                                                    multiple sclerosis; whereas the more recently introduced DNA-based
induce antibodies in serum and in tracheal lung wash. Currently the
                                                                                    vaccines have been developed for alleviating allergy such as asthma.
approach of intranasal immunization using avian influenza virus
                                                                                    However, in general, such vaccines work mainly by redirecting immune
antigen-antibody complex is studied in chickens to evaluate whether
                                                                                    polarization (Th1 vs. Th2) or inducing peripheral deletion and are
similar immune response can be induced in birds.
                                                                                    limited to passive immune regulatory mechanisms. Methods: Co-
                                                                                    administration of the DNA-protein regimens into animal has been
References:
                                                                                    employed to induce an antigen specific T cell suppression has been
1. Tumpey T.M., M.Renshaw, J.D. Clements,and J.M.Katz. Mucosal
                                                                                    evaluated by MLR, DTH, cytokine profiles, adoptive transfer and FACS
   delivery of inactivated influenza vaccine induces B-cell-dependent
                                                                                    assays. Results: The co-administration did not produce enhanced
   heterosubtypic cross-protection against lethal influenza A H5N1
                                                                                    immunity, but rather resulted in impaired delayed type hypersensitivity
   virus infection. J.Virol 2001;75:5141-5150.
                                                                                    and antigen-specific T cell proliferation, while the levels of total IgG
2. Qu Di, BJ Zheng, Xin Yao, et al. Intranasal immunization with
                                                                                    remain the same. Adoptive transfer of T cells from those co-immunized
   inactivated SARS-CoV(SARS-associated coronavirus) induced local
                                                                                    animals conferred the suppressive activity to naïve and active immunized
   and serum antibodies in mice. Vaccine 23(2005):924-31.
                                                                                    recipient animals, suggesting the involvement of suppressor T cells. The
                                                                                    elicited suppressor T cells are antigen non-specific and able to inhibit
                                                                                    the activation of allogenic T cells and are also correlated with a shift of

P2        Flagellin is an Effective Mucosal Adjuvant in the Development
          of a Protective Immune
          Response Against Yersinia pestis
                                                                                    cytokine balance, as reflected by an elevated level of IL-10 and reduced
                                                                                    level of IFN-_ or IL-2. Conclusion: Our results illustrate the
                                                                                    complexity of the interplay between DNA and protein vaccines during
          A. N. Honko, S. B. Mizel                                                  immunization and are the first study to demonstrate that co-
          Microbiology and Immunology, Wake Forest University School of Medicine,   immunization with DNA- and protein-based vaccines may represent a
          Winston-Salem, NC.                                                        novel means for inducing active suppression against untoward
                                                                                    immunity.
    Background: Pneumonic plague is a highly transmissible form of
Yersinia pestis infection that is fatal without immediate medical                   References:
treatment. Although the shift in vaccine development from complete                  1. Amara, R. R., F. Villinger, et al., Control of a Mucosal Challenge and
pathogens to individual antigens has led to safer vaccines, efficacy has,              Prevention of AIDS by a Multiprotein DNA/MVA Vaccine.
in many cases, been markedly reduced. Vaccine adjuvants are necessary                  SCIENCE 2001, 292:69
to promote strong adaptive responses to recombinant protein antigens.               2. Horner, A., J. Van Uden, J. Zubeldia, D. Broide, and E. Raz. DNA-
We evaluated the efficacy of a recombinant mucosal vaccine consisting                  based immunotheraputics for the treatment of allergic disease.
of the F1 antigen of Y. pestis and Salmonella flagellin as an adjuvant.                Immunol Reviews 2001, 179:102.


68
   on Vaccine Research
                               ABSTRACTS OF INVITED PRESENTATIONS
                           ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
          Aluminum Phosphate is an Active Adjuvant for CRM197                           b) earlier antibody responses (Flu and Hepatitis A) and
P4        Pneumococcal Conjugate Vaccine (PnC) in Infants
          S. Lockhart1, W. Watson1, P. Fletcher2, A. Leeper3, S. Edwards4,
                                                                                        c) the need of much less antigen to obtain a good antibody response
                                                                                          (Flu and Rabies)
          M. McCaughey5, A. Dunning1, D. Sikkema1, G. Siber1                                Since rat and monkey cells are significantly less immunostimulated
          1
            Wyeth Research, Pearl River, NY, 2Woolwell Surgery, Plymouth, UNITED        in vitro by PyNTTTTGT ODNs than human cells, it can be predicted
          KINGDOM, 3Grove Surgery, Thetford, UNITED KINGDOM, 4North Cardiff             an excellent performance for human vaccination. Moreover, preclinical
          Medical Centre, Cardiff, UNITED KINGDOM, 5Health Centre, Randalstown,         trials have demonstrated that IMT504 is an extremely safe drug.
          UNITED KINGDOM.

    Background. This study was designed to compare the
immunogenicity and reactogenicity of combined 9-valent
pneumococcal (9vPnC) and meningococcal C (MnCC) CRM197
conjugates with (AlPO4 [+]) or without AlPO4 (AlPO4 [-]) in human                       P6        Novel Peptide Nanoparticles: A Platform for Vaccine Design
                                                                                                  D. Tropel1, A. C. Tissot2, C. Schellekens2, S. K. Raman1, A. Graff1, G.
                                                                                                  Machaidze1, M. F. Bachmann2, P. Burkhard3
infants. Methods. 224 UK infants were randomized to 9vPnC/MnCC
at 2, 3, 4 and 12 months formulated as AlPO4 [+] or AlPO4 [-].
                                                                                                  1
                                                                                                    M.E Mueller Institute, Biozentrum, Basel, SWITZERLAND, 2Cytos Biotechnology,
Subjects also received Infanrix-Hib and oral polio vaccine. Ab was                                Schlieren, SWITZERLAND, 3The Institute of Materials Science, University of
assayed by ELISA. Results. IgG Ab responses were higher with AlPO4                                Connecticut, Storrs, CT.
group for MnC and most PnC serotypes after two or more doses. GM
[Ab] after 3 doses in 94 evaluable AlPO4 (+) and 91AlPO4 (-)                                Background: We have recently described structure-based design of a
recipients were:                                                                        novel type of nanoparticles, which self-assemble from single polypeptide
                                                                                        chains. Such nanoparticles have a regular polyhedral symmetry and a
        PnPs9    4       5       6B      9V    14       18C     19F    23F MnCPs        diameter similar to small viruses, so we have investigated the possibility
AlOP4 + 2.46*    2.08*   1.15*   1.05    1.43* 4.69     1.40    2.94   1.19 9.63*       to use them as a repetitive antigen display system. Methods: We have
                                                                                        established a recombinant Escherichia coli protein expression system to
AlPO4 - 1.79     1.41    0.84    0.88    1.06    3.87   1.17    2.99   0.95 7.13
                                                                                        easily produce nanoparticles displaying an antigenic Salmonella epitope.
*significant at p <.05                                                                  These nanoparticles were injected to four mice at day 0 and 14 and
Reactions: AlPO4 (+) 9vPnC/MnCC induced significantly more                              antibody production was studied by Elisa assay. Results: We have
erythema, swelling and tenderness than AlPO4 (-) but similar rates to                   constructed an expression vector for Escherichia coli, which allowed the
Infanrix-Hib. No significant differences were seen in fever, and other                  fusion between the DNA sequences coding for an antigenic Salmonella
systemic reactions after any dose. Conclusions. AlPO4 increased Ab                      epitope and the peptide forming the nanoparticle. The resulting His-
responses to most PnC serotypes and MnCC in human infants. Local                        tagged polypeptide was purified via metal affinity chromatography
reactions were higher with AlPO4 but similar to those with licensed                     under denaturing conditions and correct self assembling into
vaccines.                                                                               nanoparticles was obtained by successive dialyses. The serum of mice
                                                                                        immunized with nanoparticles displaying Salmonella epitope was
References:                                                                             analyzed at day 21. High titers of epitope-specific IgG were detected,
1. Wernette CM, Frasch CE, Madore D, et al. Enzyme-linked                               suggesting a strong humoral immune response. Conclusions: Since
   immunosorbent assay for quantitation f human antibodies to                           other peptide epitopes can easily be displayed on the surface of these
   pneumococcal polysaccharides. Clin Diagn Lab Immunol                                 nanoparticles this novel technology represents a versatile platform for
   2003;10(4):514-519                                                                   efficient vaccine design. Furthermore, since the nanoparticles are built
2. Sikkema DJ, Friedman KE, Corsaro B, et al. Relationship between                      from protein domains this allows for a highly specific design in terms of
   serum bactericidal activity and serogroup-specific immunoglobulin                    shape, size and stability.
   G concentration for adults, toddlers, and infants immunized with
   Neisseria meningitidis serogroup C vaccines. Clin D                                  Reference:
                                                                                        1. Lechner F, Jegerlehner A, Tissot AC, et al. Virus-like particles as a
                                                                                           modular system for novel vaccines. Intervirology 2002; 45:212-217


P5       PyNTTTTGT Oligonucleotide IMT504 is a Potent Vaccine Adjuvant
          A. D. Montaner1, F. Elias2, J. M. Rodriguez2, J. Flo2, R. Lopez2, J.
          Zorzopulos1
          1
            Instituto de Investigaciones Biomédicas, Fundación Pablo Cassará., Buenos
          Aires, ARGENTINA, 2Immunotech S.A., Buenos Aires, ARGENTINA.
                                                                                        P7        Native Display of An HIV Tat Peptide on the Surface of Human
                                                                                                  Ferritin
                                                                                                  C. Li, E. Soistman, D. C. Carter
                                                                                                  New Century Pharmaceuticals, Inc, Huntsville, AL.
    PyNTTTTGT oligodeoxinucleotides (ODNs) cause activation,
proliferation and immunoglobulin secretion on B cells, and the
                                                                                            In order to improve immunogenicity and efficacy, vaccination
expression of co-stimulatory molecules on plasmacytoid dendritic cells
                                                                                        strategies are becoming increasingly sophisticated. Recently, we have
of primates and rats (1)
                                                                                        developped a protein nanoparticle based technology platform for the
    The goal of this study was to investigate the adjuvant properties of
                                                                                        presentation of protein and peptide immunogens. As a demonstration,
PyNTTTTGT prototype IMT504 ODN on different human vaccines
                                                                                        an HIV-1 Tat peptide has been engineered and expressed in E.coli. as a
such as Flu, Hepatitis B, Hepatitis A and Rabies.
                                                                                        ferritin fusion protein.SDS-PAGE and Transmission Electron
Addition of IMT504 to commercial vaccines, compared to the antigen
                                                                                        Microscopy studies confirmed proper capsid assembly and orderly
  alone, resulted in:
  a) higher antibody responses (Flu, Hepatitis B and Hepatitis A)                                                                                                 (continued)


                                                                                                                                                                            69
        Eighth Annual Conference
                               ABSTRACTS OF INVITED PRESENTATIONS
                           ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
display of the HIV Tat prptide on the surface of this protein                       References:
nanoparticle. Animal studies demonstrated that this chimeric particle               1. Bah E, Parkin DM, Hall AJ, et al. Cancer in the Gambia: 1988-97.
elicits a potent humoral response orders of magnitude greater than                     Br J Cancer 2001;84:1207-14
conjugation of the peptide with KLH. After final immunization, the                  2. Whittle HC, Jaffar S, Wansborough M, et al Observational study of
serum immune response lasts more than three months without noteble                     vaccine efficacy 14 years after trial of hepatitis B vaccination in
loss of the activity. Concentrations of fusion protein which are 100                   Gambian children. BMJ 2002;325:569-72
times (Mole ratio) less than that utilized to immunize with soluble Tat
peptide alone, are capable to induce considerable immune response.
Preliminary studies using an HIV virus Tat-based neutralization assay
and the antibody generated with this chimeric particle indicated                             T Cell Responses to Hepatitis B Vaccine
neutralization of the virus. Orally immunized animals with this fusion
protein also produce high titer anti-Tat antibodies. These results
                                                                                    P9       M. S. Hayney, N. A. Wiegert
                                                                                             University of Wisconsin School of Pharmacy, Madison, WI.
indicated that the protein nanoparticle (ferritin)-mediated delivery of
HIV Tat peptide can dramatically increase the antigen accessibility to                  Background: T cell function is critical to the biology of
host immune system and induce specific neutralizing antibodies. Oral                immunization. The hypotheses are that the T cell responses to hepatitis
activity suggested that peptide expressed on this platform can resist               B vaccine will be CD4+ cell dominant and that the vigor of the
enzymatic degradation and be absorbed into the bloodstream                          responses will correlate with cytokine genotype. Methods: Ten healthy
efficiently. Further examples which include applications for influenza,             hepatitis B vaccine responders were enrolled. Peripheral blood
malaria and foot and mouth disease are in development.                              mononuclear cells (PBMC) and CD4+ and CD8+ populations were
                                                                                    isolated for the trans-vivo delayed-type hypersensitivity (DTH) assay
References:                                                                         from blood samples obtained. PBMC alone, CD4+ or CD8+
1. Kramer RM, Li C, Carter DC, Stone MO and Naik RR. Engineered                     lymphocytes and antigen presenting cells alone, with hepatitis B surface
   protein cages for nanomaterial synthesis. Journal of American                    antigen (HBsAg) and with HBsAg and antibodies to interferon _
   Chemistry Society. 2004; 126(41): 13282-13286.                                   (IFN_), interleukin-4 (IL), or IL-10 were injected into the footpad of
2. Morris CB, Thanawastien A, Sullivan DE and ClementsJD.                           immunodeficient mice. The resulting swelling is an index of human T
   Identification of a peptide capable of inducing an HIV-1Tat-specific             cell sensitization. Cytokine genotyping of IFN_, IL-4 and IL-10 was
   CTL response. Vaccine.2002; 20: 12-15                                            done using the polymerase chain reaction. Results: The mean response
                                                                                    by CD4+ cells (35.0+6.6 x10-4 inches) and CD8+ cells (23.5+6.4 x10-4
                                                                                    inches) to HBsAg were similar (p>0.2; paired t test). The CD4+ cell
                                                                                    responses depended on IL-4 and IL-10 such that the vigor of the

P8       Protection Against Hepatitis B Carriage Following Infant
         Vaccination May Fall With Age
         M. E. Mendy, M. A. B. van der Sande, P. Waight, P. Rayco-Solon, P. Hutt,
                                                                                    responses decreased when these cytokines were inhibited (CD4+
                                                                                    35.0+6.6 x10-4 inches vs. CD4+ antiIL-4/10 18.0+3.3x10-4 inches;
                                                                                    p<0.03) The CD8+ cell response was not consistently regulated by
         T. Fulford, C. Doherty, S. McConkey, D. Jefferies, A. Hall, H. Whittle     cytokines. Those with high IL-10 producing genotypes were particularly
         Viral Disease Programme, Medical Research Council, Banjul, GAMBIA.         dependent on Th2 cytokines for DTH response (low producers
                                                                                    32.5+7.5x10-4 inches vs. high producers 14.4+2.7x10-4 inches p<0.03).
    Background. Chronic carriage of HBV is a major risk factor for                  Conclusion: Hepatitis B immunization elicits both CD4+ and CD8+
liver cirrhosis and hepatocellular carcinoma. Infant vaccination has                immune responses. The vigor of the CD4+ response is regulated by Th2
been effective in preventing horizontal transmission in early                       cytokines—IL-4 and IL-10.
childhood. It is not known whether this protection will be maintained
against sexual transmission in early adulthood. Methods. Infant                     References:
vaccination was introduced in The Gambia in 1984. Serological                       1. VanBuskirk AM, Burlingham WJ, Jankowska-Gan E, et al. Human
assessment of 1099 fully vaccinated participants between the ages of 1                 allograft acceptance is associated with immune regulation. J. Clin.
and 24 was conducted in 2003, in order to determine vaccine efficacy                   Invest. 2000;106:145-55
(VE) against infection and chronic carriage two decades post                        2. Hahn AB, Kasten-Jolly JC, Constantino DM, et al. TNFa, IL-6,
introcudction of vaccination. The core and surface antibody tests were                 IFNg, and IL-10 gene expression polymorphisms and the IL-4
performed by radio immunoassay or ELISA and HBsAg was detected                         receptor a-chain variant Q576R: Effects on renal allograft outcome.
by RPHA or immunochromatography. Data were entered and                                 Transplantation 2001;72:660-5
validated in access 2000 and data analysis was done using Stata 8.
Results. Overall VE against infection and chronic carriage was 83.4%
(95%CI 79.8-86.6) and 96.5% (93.9-98.9) respectively; against
cumulative infection and carriage it was 78.0% (74.1-81.7) and 95.0%
(92.0-97.7). However, both VE and surface antibody levels declined
with age. Less than half of the vaccinees still had detectable antibody
                                                                                    P10       T Cell Responses Following Hepatitis A Immunizaton
                                                                                              M. S. Hayney, N. A. Wiegert
                                                                                              University of Wisconsin School of Pharmacy, Madison, WI.
15 years after vaccination. Conclusions. HBV vaccination in early life
can provide long-lasting protection into early adulthood, in spite of
                                                                                        Background: Interferon _ (IFN_) and interleukin (IL)-10 are
loss of antibody levels and an increasing rate of core antibody
                                                                                    produced with hepatitis A infection and following immunization. The
conversion, but decreases progressively with age. The role of sub-
                                                                                    hypotheses are that the T cell responses to hepatitis A vaccine will be
clinical boosting, and the necessity of a booster vaccine, need to be
                                                                                    CD4+ cell dominant and that the vigor of the responses will correlate
evaluated.
                                                                                    with cytokine genotype. Methods: Eight healthy hepatitis A
                                                                                    seronegative individuals were immunized with hepatitis A vaccine.

70
   on Vaccine Research
                                ABSTRACTS OF INVITED PRESENTATIONS
                            ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
Peripheral blood mononuclear cells (PBMC) and CD4+ and CD8+                              References:
populations were isolated for the trans-vivo delayed-type                                1..Patrick DM, Bigham M, Ng H, White R,et all. Elimination of acute
hypersensitivity (DTH) assay from blood samples obtained 10-12 days                         hepatitis B among adolescents after one decade of an immunization
after immunization. PBMC alone, CD4+ or CD8+ lymphocytes and                                program targeting Grade 6 students. Pediatr Infect Dis J.
antigen presenting cells alone, with hepatitis A antigen (hepA), and                        2003;22(10):874-877
with hepA and antibodies IFN_, IL-4, or IL-10 were injected into the                     2. Mele A, Stroffolini T, Zanetti A, et al. Hepatitis B in Italy: where are
footpad of immunodeficient mice. The resulting swelling is an index                         we ten years after the introduction of mass vaccination? J Med
of T cell sensitization. Cytokine genotyping of IFN_, IL-4 and IL-10                        Virology 2002;67:440-443
was done using the polymerase chain reaction. Results: The mean
response by CD4+ cells (26.1+12.4 x10-4 inches) and CD8+ cells
(16.7+9.6 x10-4 inches) to hepA vaccine virus were similar (p=0.4;
paired t test). The CD8+ cell response was regulated by IL-4 and IL-
10 (CD8+ 8+14 vs. CD8+ anti-IL-4/10 24+15 x10-4 inches; p<0.05;
paired t test). Additionally, all four individuals with intermediate to
                                                                                         P12       Antibody Responses to Vaccinia Membrane Proteins Following
                                                                                                   Smallpox Vaccination
                                                                                                   S. Lawrence1, K. Lottenbach2, F. Newman2, M. Buller2, C. Bellone2,
high IFN_, IL-4 and IL-10-producing genotypes maintained or                                        S. Koehm2, S. Stanley, Jr.1, R. Belshe 2, S. Frey 2
increased CD8+ cell responses to hepA with anti-IL-10 indicating the                               1
                                                                                                     Washington University, St. Louis, MO, 2 Saint Louis University, St. Louis, MO.
role of IL-10 in regulating the immune response (p<0.05; Fisher’s
exact). Conclusion: Hepatitis A immunization elicits CD4+ and                                Background: Vaccinia virus extracellular enveloped virion (EEV)
CD8+ immune responses. The vigor of the CD8+ response is                                 and intracellular mature virion (IMV) membrane proteins are potential
regulated by IFN_, IL-4 and IL-10.                                                       candidates for use in smallpox subunit vaccines. Human antibody
                                                                                         responses to these proteins after vaccinia vaccination are not known.
References:                                                                              Methods: Paired (pre- and 28-days post-vaccination) sera from 29
1. VanBuskirk AM, Burlingham WJ, Jankowska-Gan E, et al. Human                           vaccinia-naïve and 29 non-naïve adults vaccinated with live vaccinia
   allograft acceptance is associated with immune regulation. J. Clin.                   virus (Dryvax®) were examined for presence and titers of anti-EEV
   Invest. 2000;106:145-55                                                               protein (B5R, A33R) and anti-IMV protein (L1R, A27L) antibodies by
2. Hayney MS, Buck JM and Muller D. Production of interferon g                           ELISA. Chi-square, non-parametric, and t-tests were used to compare
   and interleukin-10 after inactivated hepatitis A immunization.                        antibody responses. Results: In naïve vaccinees, post-vaccination
   Pharmacotherapy 2003;23:431-5                                                         antibodies were detected in 69.0% [B5R], 100% [A33R], 93.1%
                                                                                         [A27L], and 62.1% [L1R] of naïve vaccinees. In non-naïve vaccinees
                                                                                         pre-existing antibodies were present in 72.4% [B5R], 58.6% [A33R],
                                                                                         40.7% [A27L], and 6.9% [L1R], and were boosted ≥4-fold in 62.1%
          Impact of a School Based Hepatitis B Immunization Program in a
P11       Low Endemic Area
          V. Gilca, PhD1, B. Duval, MD2, N. Boulianne, MSc2, R. Dion, MD2,
                                                                                         [B5R], 34.5% [A33R], 59.3% [A27L], and 3.5% [L1R]. Interestingly,
                                                                                         anti-A33R responses were more vigorous in naïve vaccinees (10.0- vs
                                                                                         2.8-fold geometric mean titer boost for naïve vs. non-naïve, p<0.001),
          G. D. Serres, PhD3
                                                                                         resembling neutralizing antibody responses (88.2- vs. 14.3-fold boost,
          1
            Centre de recherche du Centre Hospitalier Universitaire de Québec, Quebec,
                                                                                         p<0.001), while anti-B5R responses were more robust in non-naïve
          PQ, CANADA, 2Institut National de Santé Publique du Québec, Quebec, PQ,
                                                                                         vaccinees (3.1- vs. 6.5-fold boost, p=0.010), similar to whole virus
          CANADA, 3Laval University, Quebec, PQ, CANADA.
                                                                                         binding (ELISA) antibodies (6.3- vs. 15.6-fold boost, p<0.001).
                                                                                         Conclusions: Our findings suggest that Dryvax® vaccination elicits
    Background: In 1994, a school-based routine HB immunization
                                                                                         anti-EEV and anti-IMV membrane protein antibody responses in most
program was implemented in Quebec in grade 4 children in parallel
                                                                                         naïve vaccinees. Except for anti-L1R, these specific antibody responses
with increased vaccination of high risk groups. Ten years later we
                                                                                         appear durable and are substantially boosted by re-vaccination. Further
conducted a study to assess the impact of the program, vaccine
                                                                                         correlation with other immunologic and clinical parameters is needed.
failures, and number of cases that would have been prevented by an
infant program. Methods: Acute HB cases reported for 1994-2003
                                                                                         References:
were retrieved from the provincial Register of Notifiable Diseases.
                                                                                         1. Frey SE, Newman FK, Yan L, Belshe RB. Response to smallpox
Detailed information on risk factors and vaccination status were
                                                                                            vaccine in persons immunized in the distant past. JAMA
extracted from regional Public Health Department files for all 0-20
                                                                                            2003;289:3295-9.
year-old cases. Results: Between 1994 and 2003, a 4-fold HB
                                                                                         2. Belshe RB, Newman FK, Frey SE, et al. Dose-dependent
incidence decline was observed in the general population, 10-fold in
                                                                                            neutralizing-antibody responses to vaccinia. J Infect Dis
the 10-20 year-olds. In the same period, from 37 cases observed in
                                                                                            2004;189:493-497.
10-20 year-olds, 30 (81%) cases were in older cohorts not covered by
the school immunization program. In this age group, 32 cases were
non vaccinated, one case fully vaccinated, and 4 others incompletely
vaccinated. From 45 cases notified in under 10 year-old children,
24 (53%) were born outside Canada and 14 (31%) were born from
HBsAg positive mothers. Up to 26 (58%) cases in children under
10 years old could have been prevented by an infant immunization
program in Quebec. Conclusions: The preteen vaccination program is
highly effective. An infant program would bring some additional
benefits.
                                                                                                                                                                       (continued)


                                                                                                                                                                                 71
         Eighth Annual Conference
                               ABSTRACTS OF INVITED PRESENTATIONS
                           ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
          Serum Neopterin for Early Assessment of Severity of Severe                inhibition ELISA protocol are linear, reproducible and cover a large
P13       Acute Respiratory Syndrome
          J. W. Y. Choi
                                                                                    dynamic range.

          Department of Microbiology, The University of Hong Kong, Pokfulam, Hong   References:
          Kong Special Administrative Region of China.                              1. Harris, SL, King, WJ, Ferris, W, Granoff, DM. Age-related disparity
                                                                                       in functional activities of human group C serum anticapsular
    Neopterin concentrations were determined in serum samples from                     antibodies elicited by meningococcal polysaccharide vaccine Infect.
129 severe acute respiratory syndrome (SARS) patients and 156                          Immun. 2003;71(1):275-286.
healthy blood donors. In the patients with confirmed SARS, an early                 2. Goldblatt, D, Borrow, R, Miller, D. Natural and vaccine-induced
neopterin elevation was detected already at the day of onset of                        immunity and immunologic memory to Neisseria meningitidis
symptoms and rose to a maximum level of 122.5 nmol/L 3 days after                      serogroup C in young adults. J. Infect. Dis., 2002; 185(3):397-400.
the onset. The mean neopterin concentrations were 34.2 nmol/L in
acute sera of SARS patients, 5.1 nmol/L in convalescent sera and 6.7
nmol/L in healthy controls. Serum neopterin level in SARS patients
                                                                                              Quantitation of Human Serum Immunoglobulin G Against O-Acetyl
was associated with fever period and thus the clinical progression of
the disease. After steroid treatment, decrease of neopterin level
demonstrates that it is a useful marker of inflammatory activity of
                                                                                    P15       Positive and O-Acetyl Negative Serogroup W135 Meningococcal
                                                                                              Capsular Polysaccharide
SARS. Together with a 100% of sensitivity within 9 days after the                             P. C. Giardina1, E. Longworth2, R. Borrow2, P. Fernsten1
onset of symptoms, serum neopterin may allow early assessment of the                          1
                                                                                                Applied Immunology and Microbiology, Wyeth, Pearl River, NY,
severity of SARS and evaluation of the treatment efficacy.                                    2
                                                                                                Meningococcal Reference Unit, Manchester Medical Microbiology Partnership,
                                                                                              Health Protection Agency, Manchester, UNITED KINGDOM.
References:
1. Peiris JSM, Lai ST, Poon LLM, et al. Coronavirus as a possible                       Background: The capsule of Neisseria meningitidis serogroup W135
   cause of severe acute respiratory syndrome. Lancet 2003;361:1319-                is expressed as both O-acetyl positive (OA+) and O-acetyl negative (OA-
   1325                                                                             ) forms. The purpose of this study is to understand the impact of OA
2. Fahey JL, Taylor JM, Detels R, et al. The prognostic value of                    status on serological measurements of anti-W135 IgG antibodies.
   cellular and serologic markers in infection with human                           Methods: Sera from 28 adults immunized with a licensed
   immunodeficiency virus type 1. N Engl J Med 1990;322:166-172                     meningococcal polysaccharide vaccine (Menomune; A, C, Y and W135
                                                                                    vaccine, Aventis) were analyzed for W135-specific serum antibody
                                                                                    concentrations against the standard reference serum, CDC1992, by
                                                                                    enzyme-linked immunosorbent assay (ELISA) and for functional killing
                                                                                    activity by serum bactericidal assay (SBA). Results: A concentration of
P14       Determining Avidity for Anti-polysaccharide Antibodies
          S. Harris, J. Tam, P. Fernsten;
          Vaccines Research, Wyeth, Pearl River, NY.
                                                                                    10.13_g/ml IgG against OA- antigen was established for CDC1992 by
                                                                                    cross-standardization against OA+ antigen (16.2_g/ml). Overall, serum
                                                                                    IgG against OA+ antigen (geometric mean concentration (GMC) =
    Background: Antibody avidity is an important characteristic of                  7.16_g/ml) was higher compared to OA- antigen (GMC = 2.82_g/ml).
protective immunity. One advantage of polysaccharide-conjugate                      However, seven specimens contributed disproportionately to this
vaccines over polysaccharide vaccines is the ability to elicit higher               difference. These sera were also distinguished by the inability of fluid
avidity antibodies which may correlate with B cell memory. A                        phase OA- antigen to compete for antibody binding to OA+ solid phase
chaotropic ELISA is commonly used for assessing avidity indices.                    antigen. Although there were no overall differences in SBA titers against
However, chaotropes disrupt secondary and tertiary antibody and                     OA+ and OA- target bacteria (GMT = 9642 and 9045, respectively),
antigen structure as well as antibody-antigen interactions. As a result,            three specimens showed relatively large differences, which may reflect
the avidity index may not correlate to antibody avidity alone.                      different epitope specificities. Conclusion: The relationship between
Methods: Avidity (KD) can be expressed as the concentration of                      capsule-specific IgG concentrations measured by ELISA against OA+
antigen needed to decrease antibody binding by 50% (IC50) at                        and OA- W135 antigens is serum specific and does not reflect the
equilibrium. Thus, IC50 data from inhibition ELISAs using soluble                   functional (killing) activity for some specimens, in vitro.
antigen to inhibit antibody binding to immobilized antigen can be
converted to avidity constants if the inhibitor concentration is                    References:
expressed in terms of moles of epitope. Polysaccharide epitope                      1. Elie, C. M., P. K. Holder, S. Romero-Steiner, and G. M. Carlone.
molarity can be determined from binding stoichiometry meaurements                      2002. Assignment of Additional Anticapsular Antibody
derived from microcalorimetry titration experiments. Results: We have                  Concentrations to the Neisseria meningitidis Group A, C, Y, and W-
developed an inhibition ELISA to measure antibody avidity to the                       135 Meningococcal Standard Reference Serum CDC1992. Clin
capsular polysaccharide (PS) of Neisseria meningitidis group C (MnC).                  Diagn Lab
For two MnC PS monoclonal antibodies, binding occurs every 10.5                     2. Giardina, P. C., R. E. Evans, D. J. Sikkema, D. Madore, and S. W.
carbohydrate repeat units. We have determined avidity constants for                    Hildreth. 2003. Effect of antigen coating conditions on enzyme-
several sera from adults immunized with MnC PS vaccine and from                        linked immunosorbent assay for detection of immunoglobulin G
100 children immunized with MnC PS-conjugate vaccine. The avidity                      antibody to Neisseria meningitidis serogroup Y and W135 caps
constants for the adult sera tested range from 1.70 nM to 1173 nM
and for the pediatric sera from 118 nM to 1220 nM. Comparison with
published chaotropic ELISA data suggests the inhibition ELISA has a
larger dynamic range. Conclusions: Avidity constants from an


72
   on Vaccine Research
                               ABSTRACTS OF INVITED PRESENTATIONS
                           ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
          Evaluating the Influences of Glycosylation on the Immunogenicity             6 were HIV-1 envelope proteins. Conclusion: A RAFE system was
P16       of the Ebola Virus Glycoprotein
          W. E. Dowling1, R. J. Hogan2, E. Thompson3, J. Paragas1, G. Bush1,
                                                                                       established which could be valuable in generating vaccines for the
                                                                                       control of HIV infection.
          J. Smith1, W. Capps1, L. Grey1, C. Badger1, C. S. Schmaljohn1
          1
            Virology, USAMRIID, Fort Detrick, MD, 2Infectous Diseases, University of   Reference:
          Georgia, Athens, GA, 3Cder, FDA, Rockville, MD.                              1. Chen X, Scala G, Quinto I, et al. Protection of rhesus macaques
                                                                                          against disease progression from pathogenic SHIV-89.6PD by
    Background: The requirements for protective immunity against                          vaccination with phage-displayed HIV-1 epitopes. Nature Med 2001;
Ebola virus infection are not completely understood, although the                         7(11):1225-1231
importance of antibody and T-cell responses against the glycoprotein
(GP) have been demonstrated (Reviewed in 1). Numerous studies of
other viral systems have shown that glycosylation plays a major role in
the structure, function, and antigenicity of glycoproteins (2). Methods:
We generated a series of glycosylation mutants of GP to assess the                     P18       Toll-like Receptor 4 Plays Role in Activating Dendritic Cells by
                                                                                                 Necrotic Cells
                                                                                                 C. Kang, J. Choi, S. Lee, H. Moon, S. Seong
importance of glycosylation to its expression and immunogenicity.
These mutated genes were cloned into a mammalian expression plasmid                              Microbiology and Immunoogy, Seoul National University College of Medicine,
and tested for expression in transfected cells. Mice were vaccinated with                        Seoul, REPUBLIC OF KOREA.
each construct three times by gene gun. Sera were collected after each
inoculation and were tested for antibody titers by ELISA. Ten mice per                     It is currently thought that immune responses are initiated by
group were challenged with mouse-adapted EBOV Zaire. The remaining                     pathogen-associated molecular patterns (PAMP) or by damage-associated
mice were killed, and then splenocytes were harvested, stimulated with                 molecular patterns (DAMP). However, these two groups of molecules
pools of overlapping GP peptides, and assessed for interferon-gamma                    might not be mutually exclusive. Many of them might be part of an
production by ELISPOT. Results: The different glycosylation mutants                    evolutionarily ancient alert system in which the hydrophobic portions
elicited varying ELISA titers and T-cell responses in vaccinated mice. In              (Hyppos) of biological molecules act, when exposed, as universal DMAP
particular, the absence of one of the glycosylation sites in GP2 had a                 to initiate repair and immunity.
significant impact on antibody responses, T-cell responses, and                            Because life on earth originated in water, Hyppos are normally hidden
protection after challenge with EBOV. Conclusions: These results                       from the aqueous environment by conformational folding, by help from
indicate that alterations in the glycosylation of GP can affect its                    regulatory molecules or by virtue of their insertion into a lipid bilayer.
immunogenicity and should be considered in the design of GP-based                      Because exposed Hyppos rapidly form non-productive or even toxic
EBOV vaccines and therapeutics.                                                        aggregates, organisms expend a great deal of metabolic energy to prevent
                                                                                       such exposure and maintain homeostasis. If, however, cell should die
References:                                                                            necrotically, it will release several Hyppos into its immediate
1. Feldmann H, Jones S, Klenk HD and Schnittler HJ. Ebola virus:                       environment, including membrane lipids, integral membrane molecules,
   from discovery to vaccine. Nat. Rev. Immunol. 2003; 3;677-85.                       immature proteins, heat shock proteins, etc.
2. Wei X, Decker JM, Wang S, et al. Antibody neutralization and escape                     In this study, we showed that Toll like receptor 4 recognize DAMP.
   by HIV-1. Nature 2003; 422;307-12.                                                  Lipids activated dendritic cells. The activation of DC by necrotic cells
                                                                                       (NC) was inhibited by apolipoproteins. DCs from TLR4 knockout mice
                                                                                       were less responsive to NC than wild type DC in terms of costimulatory
                                                                                       molecule expression, IL12p40 secretion and naïve T cell activation. The

P17       The Establishment of a Restriction Assorted Fragments Expression
          (RAFE) System for Vaccine Development of HIV-1B Subtype
          R. Shi1, W. Zheng2, J. Liu1, L. Li1, W. Ma1
                                                                                       chemokine expressions of DC by NC were controlled by TLR4 pathways.
                                                                                       For these reasons, we suggest that Hyppos from NC are evolutionarily
                                                                                       ancient DAMP and TLR4 contributes in activating DC by Hyppos.
          1
            Institute of Molecular Biology, NanFang Medical University, Guangzhou,
          CHINA, 2South China Genomics Research Center, Guangzhou, CHINA.              Reference:
                                                                                       1. Seong SY, Matzinger P. Hydrophobicity; Damage-associated
    Background To establish a universal RAFE system which is simpler                      molecular pattern that initiates innate immune responses. Nature Rev
than random peptide libraries (RPL) screening for the development of                      Immunol 2004; 4: 469-478
HIV recombinant vaccines. Method The genome of HIV-1B subtype
U26942 was digested with Sau3A I into 26 restriction fragments.
Specially designed universal adapters were ligated with each fragments so
                                                                                                 Construction of Recombinant BCG Based HIV-1 epitope Delivery
that it could express all of the three possible reading frame peptides by
sense and anti-sense orientations. Such fragments were cloned into
Vector pFAB5C and verified for surface display endorsed by a CMV
                                                                                       P19       System and Evaluation of its Immunogenicity in a Murine Model
                                                                                                 A. Vivekanandhan, N. Sujatha, P. Narayanan
promoter. This surface display library was screened by ELISA and was                             Immunology, Tuberculosis Research Centre, Chennai, INDIA.
further used as a pool of HIV phage-display fusion peptides, which were
printed into a microarray. Such peptide pool was further injected into                    Background: AIDS vaccine is a global emergency. Intense efforts are
experimental mice, sera of experimental mice as well as negative controls              under way to identify protective epitopes and novel delivery vehicles.
were collected and applied upon the microarray for detection. Results                  Grafting an epitope from an immune unfriendly environment to an
Over 1/2 among the 156 possible peptides could be expressed as fusion                  immune friendly environment forms the basic of ‘epitope grafting’.
peptides on phage surface. 29 antibodies against the fusion peptides                   Methods: In this respect the present project aims at constructing an
could be detected by microarray in the experimental mice, among which                                                                                          (continued)


                                                                                                                                                                        73
         Eighth Annual Conference
                              ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
‘epitope trap vector’ using Mycobacterium tuberculosis chaperonin-10                       References:
(Cpn10) antigen as a carrier antigen. The HIV-1 PND epitope was                            1. Kofler RM, Aberle JH, Aberle SW, Allison SL, Heinz FX, Mandl CW.
selected as a test epitope.                                                                   Mimicking Live Flavivirus Immunization with a Noninfectious RNA
Two versions of the Cpn10-PND chimeric antigen were constructed and                           Vaccine. PNAS 2004; 101: 1951-1956;
expressed in M. smegmatis:                                                                 2. Kofler RM, Heinz FX, Mandl CW. Capsid Protein C of Tick-Borne
1. The replacement chimera where the PND epitope replaces the                                 Encephalitis Virus Tolerates Large Internal Deletions and is a
   Cpn10 loop and                                                                             Favorable Target for Attenuation of Virulence. J. Virol. 2002; 76:
2. The insertion chimera where the PND epitope is inserted into the                           3534-3543;
   Cpn10 loop
    Based on the expression profile p306CRC (Cpn10-PND
replacement chimera in an episomal vector with homologous promoter)                                  Serotypes, Virulence Genes, and PFGE Patterns of Escherichia
was electroporated into BCG Pasteur. The immunogenicity of the
recombinant BCG was evaluated in a murine model. Results:
                                                                                           P21       coli Strains Isolated from Piglets with Diarrhoea in Slovakia
                                                                                                     H. Vu Khac
Vaccination with rBCG expressing the PND epitope induced both                                        Department of Bacteriology, Central Viet Nam Veterinary Institute, Nha trang
cellular and humoral immune responses as measured by lymphocyte                                      City, VIET NAM.
proliferation, delayed-type hypersensitivity (DTH) reaction, cytokine
secretion, generation of memory T cells and antibody production.                               250 E.coli strains isolated form piglets were serotyped and tested for
Conclusion: In summary heat shock protein based epitope delivery                           the presence of the genes for fimbriae, intimin, enterotoxin, verotoxin,
vehicles offer novel avenues in AIDS vaccine research.                                     and EAST1 toxin by PCR. These 250 strains belonged to 90 different
                                                                                           O:H serotypes. Although 220 isolates from diarrheic piglets belonged to
Reference:                                                                                 43 different O serogroups and 77 O:H serotypes, 60.5% of isolates
1. Honda, M., K. Matsuo, et al. (1995). “Protective immune responses                       belonged to only 10 serogroups (O2, O8, O15, O54, O84, O101,
   induced by secretion of a chimeric soluble protein from a                               O141, O147, O149, and O157) and 57.7% belonged to only nine
   recombinant Mycobacterium bovis bacillus Calmette-Guerin vector                         serotypes (O8:H-, O54:H-, O84:H7, O141:H-, O141:H4, O147:H-,
   candidate vaccine for human immunodeficiency virus type 1 in small                      O149:H10, O163:H-, and ONT:H-). PCR show that 78.6% of 220
   animals.” Proc Natl Acad Sci U S A 92(23): 10693-7.                                     strains from diarrheic piglets carried genes for at least one of virulence
                                                                                           factors tested. Eighty-three (37.7%) of the 220 E. coli isolates carried
                                                                                           gene for F4, whereas genes for F18, F5/F41, F6, F17, and intimin were
                                                                                           detected in 9.1%, 3.2%, 2.7%, 1.4% and 3.2%, respectively. The gene
                                                                                           encoding for EAST1 was the most prevalent (65.4%) followed by those
P20       Extending the Capsid Deletion Approach for Favivirus Vaccine
          Development to the N-terminal Part of the Protein
          R. M. Kofler, C. W. Mandl
                                                                                           encoding for STb (49.5%), LT (41.8%), STa (12.7%), and VT2 (4.1%).
                                                                                           Among 30 strains from healthy piglets only two pathotypes, EAST1
          Clinical Institute of Virology, Medical University of Vienna, Vienna, AUSTRIA.   (26.4%) and eae (16.6%), were recovered. The results show
                                                                                           epidemiological information about the prevalence of serogoups,
    A new genetic vaccine principle for flaviviruses was recently                          serotypes, and virulence factors in porcine E. coli in Slovakia.
developed based on a non-infectious, self-replicating RNA of tick-borne
encephalitis virus (TBEV). Cells expressing a replicon, which was                          References:
derived by engineering a deletion into the TBEV RNA genome coding                          1. Blanco M, Blanco JE, Gonzalez EA, et al. Genes coding for
for the central and C-terminal parts of capsid protein C, secreted                            enterotoxins and verotoxins in porcine Escherichia coli strains
capsidless subviral particles but not whole viral particles and induced a                     belonging to different O:K:H serotyps: relationship with toxin
highly protective immune response in adult mice. To advance this                              phenotyes.Journal of Clinical Microbiology. 1997; 35:2958-2963.
genetic vaccine approach, we investigated the relevance of the region                      2. Harel J, Lapointe H, Fallara A, et al. Detection of genes for fimbrial
upstream of the original deletion for TBEV replication. This region                           antigens and enterotoxins associated with Escherichia coli serogroups
coding for the N-terminus of protein C comprises a GC-rich predicted                          isolated from pigs with diarrhoea. Journal of Clinical Microbiology.
stem loop structure of potential functional importance and, in the case                       1991; 29:745-752.
of mosquito-borne flaviviruses, contains a so-called cyclization element
(CyE) essential for RNA replication. To analyze the significance of this
region for TBEV replication, two deletions were engineered, one
extending towards the stem-loop and the other removing approximately
half of this structure and the potential CyE. Surprisingly, both mutants
showed competence for RNA replication and protein translation and
                                                                                           P22       Phase 2 & 3 Vaccine Research Agenda in the Kintampo
                                                                                                     District of Ghana.
                                                                                                     S. Owusu-Agyei
demonstrated viability and genetic stability in cell culture and suckling                            Ministry of Health, Kintampo Health Research Centre, Kintampo, GHANA.
mice. Both mutants were neurovirulent in suckling mice, but the onset
of disease symptoms was delayed. In adult mice, the mutants exhibited                          The Kintampo Health Research Centre (KHRC), is set-up to
an attenuated phenotype and induced a protective immune response.                          develop and evaluate public health interventions to influence local and
Our results demonstrate that the N-terminal protein C coding region is                     international health policies. The district population of 150,000 live in
not essential for TBEV replication, but displays a further target for the                  uniquely numbered households under a continuous demographic
generation of attenuated and immunogenic vaccine candidates for                            surveillance. An extension of active surveillance is in three adjacent
flaviviruses.                                                                              districts, leading to 600, 000 human-population under demographic
                                                                                           surveillance. This area experience annual rainfall of 1280mm. Malaria is


 74
   on Vaccine Research
                          ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
the leading cause of morbidity and mortality in the district with                          Cloning and Characterization of the Polysaccharide Biosynthetic
falciparum malaria as the predominant species. Malaria is perennial with
prevalence ranging between 45 and 84%. Parasitological resistance is
                                                                                P24        Genes for Shigella dysenteriae Serotype 1 into Salmonella
                                                                                           enterica serovar Typhi Ty21a
35% for chloroquine and 15% for sulphadoxine-pyrimethamine.                                D. Xu1, J. O. Cisar2, D. J. Kopecko1
Incidence of malaria is 8 clinical attacks per child per year, and                         1
                                                                                             FDA-CBER, Bethesda, MD, 2NIH-NIDCR, Bethesda, MD.
entomological inoculation rate is 268 infective bites per person per
year.Having carried out vaccine and drug trials in the past on the                  Shigella dysenteriae type 1 causes a severe form of shigellosis and is
immunogenicity, reactogenicity and safety of GSK Nm ACW135                      classified as a Category B bioterrorist threat agent. The
polysaccharide vaccine with Nm ACYW135 polysaccharide vaccine as                lipopolysaccharide (LPS) of S. dysenteriae 1 is essential for virulence, and
well as the efficacy and safety of Artesunate Combination Therapy trials,       there is indirect evidence that antibodies against this O-specific
KHRC is in a position to carry out large-scale community trials on              polysaccharide (O-Ps) are protective to the host. Thus, there is
promising malaria-vaccine candidates in the Kintampo district as they           considerable interest in the development of an O-Ps-based vaccine to
become available. This past experience is backed by the availability of         protect against S. dysenteriae. Previous studies showed that the
qualified scientists in KHRC including 3 epidemiologists, 3 public              determinants for the production of O antigen LPS in S. dysenteriae type
health physicians, 5 research fellows (demography/public health,                1 are distributed on the chromosome (i.e. rfb/rfc genes) and on a small
nutrition and statistics) and about 45 assistant research officers, 7 data      9-kb plasmid (i.e. rfp gene). The current studies were aimed at cloning
managers several fieldworkers; most of who have undergone GCP                   the Rfb/Rfc region from strain 1617 to define all essential genes and
training. The centre is supported by a medical laboratory that conducts         develop a biosynthetic pathway for O-Ps biosynthesis. The plasmid-
microscopy, PCR, ELISAs, hematology and biochemistry analyses.                  carried gene (i.e. the rfp-encoded galactosyl transferase) was also cloned
                                                                                from strain 1617; it’s 1.2 kb sequence was found to be >99%
                                                                                homologous to rfp previously analyzed from a different S. dysenteriae 1
                                                                                strain. Additionally, the chromosomal Rfb/Rfc region of 9 kb was
                                                                                cloned and sequenced, and found to contain 9 ORFs. Preliminary

P23        A Multiplex Real-Time PCR Assay with An Internal Control for
           Quantitative Detection of Streptococcus pneumoniae
                                                                                analysis suggests that all 9 ORFs plus rfp are necessary for biosynthesis
                                                                                of serotype 1 LPS, which is presented as core-linked LPS in the Ty21a
           A. Hu, F. Li, P. Zhao, J. S. Tam, R. Rappaport, S. Cheng             vaccine vector. We anticipate that the use of these characterized O-Ps
           Wyeth, Pearl River, NY.                                              genes in a live, attenuated Salmonella delivery system will lead to a safe,
                                                                                oral vaccine for protection against this severe form of shigellosis
    Background. A multiplex PCR assay was developed to permit timely
diagnosis of S. pneumonia in clinical specimens that often contain              Reference:
inhibitors leading to misinterpretation of PCR results. To address this         1. Xu DQ, Cisar JO, Ambulos Jr N Jr, Burr DH, Kopecko DJ.
issue, we included an internal control (IC) in our PCR procedure (1) to            Molecular cloning and characterization of genes for Shigella sonnei
enable assessment of interference, if present, in clinical specimens.              form I O polysaccharide: proposed biosynthetic pathway and stable
Methods. The green fluorescence gene (GFP) was selected as the IC and              expression in a live salmonella vaccine vector. Infect Imm
a primer/probe pair was designed for detection of the GFP using
TaqMan-based PCR. Three mono-specific PCRs, one for detection of
GFP and one each for the S. pneumoniae genes, autolysin (lytA) and

                                                                                P25
pneumolysin (ply), were combined into a single tube triplex assay.                         Pneumococcal Disease and Influenza Vaccination Acceptance
Results. The limit of detection for GFP was 2.5 fg similar to that for the                 among Health Care Workers
lytA and ply genes. More importantly, no significant differences in the                    J. Wallenfels1, J. Rames2
detection limit for all 3 genes were found in the triplex versus individual                1
                                                                                             Ministry of Health of the Czech Republic, Praha, CZECH REPUBLIC, 2Institute
mono-specific PCRs. However, when nasal specimens from 12 healthy                          of Hygiene and Epidemiology, First Faculty of Medicine, Charles University in
subjects were spiked with GFP and S. pneumoniae, about 10 fold fewer                       Prague, Praha, CZECH REPUBLIC.
copies of GFP, lytA and ply were observed. This level of interference was
overcome by pre-treating specimens with Proteinase K before PCR.                    Background: Health care workers (HCW) may be at increased risk
Conclusion. We developed a rapid and cost-effective single tube triplex         for contracting influenza, especially during nosocomial outbreaks; they
real-time PCR that includes GFP as IC and permits quantitative                  also may serve as vectors for transmitting influenza to others, including
detection of S. pneumoniae even in the presence of inhibitors.                  high-risk patients. On that account vaccination of all HCW employed
                                                                                in long-term care facilities against influenza and diseases caused by
Reference.                                                                      Streptococcus pneumoniae as well is obligatory and free of charge in the
1. Li F, et al. Rapid, sensitive and quantitiative detection of streptococcus   Czech Republic (according to valid legislation) since 2000. In spite of
   pneumoniae using triplex real-time PCR. 105th ASM Meeting,                   that many of them fail to receive the vaccines. In the hope that
   Atlanta, Georgia.                                                            knowledge of factors inhibiting HCWs‘ participation in vaccine
                                                                                programmes could help to improve vaccination rates, we conducted in
                                                                                long-term care facilities in 2003 a cross-sectional survey of HCWs‘
                                                                                knowledge, attitudes, and influenza and pneumococcal disease
                                                                                vaccination status. Methods: An anonymous, self-administered
                                                                                questionnaire (49 questions). Results: There were 1 296 respondents.
                                                                                The response rate was 69.2%. The mean age of the respondents was
                                                                                45.8 years. 86.3% were females. 52.3% were nurses. The influenza
                                                                                                                                                           (continued)


                                                                                                                                                                     75
         Eighth Annual Conference
                             ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
vaccination rate was 52.7%, the pneumococcal disease vaccination rate                                Standardized Informed Consent for Low-literacy Audiences in
was 40.3%. Avoiding influenza and pneumococcal diseases was quoted
as the most important motive for acceptance of vaccination. Believing
                                                                                           P27       African Research Environment
                                                                                                     B. E. Bekan
that immune system will protect against influenza even if not                                        Projet San Francisco, Kigali, RWANDA.
vaccinated, was identified as the most important factor associated with
refusal of influenza vaccine. Fear of side effects was identified as the                       Background Some Institutional Review Boards recommend a 6-8th
most important factor associated with refusal of pneumococcal disease                      grade level for informed consent processes in research involving human
vaccine. Conclusions: Many HCW fail to receive influenza (and                              subjects (1). “Grades” are not applicable to Africa where the literacy
pneumococcal disease) vaccine. Strategies to improve immunization                          level is below 50%. Most research is often developed in non-African
levels should address concerns about vaccine safety and efficacy,                          languages. It is important to standardize the consent form process to
misconception about prevention of influenza, barriers to vaccination,                      ensure that the meaning is understood at all literacy levels. Methods:
and the reasons for targeting healthcare workers.                                          Projet San Francisco (PSF) in Rwanda translates the consents into
                                                                                           Kinyarwanda, the main language. Videos of counselors reading the
                                                                                           consent are shown during an interactive group session, written copies
                                                                                           given to participants to consult. Counselors invite questions that

P26       Burden of Invasive Disease Caused by Haemophilus influenzae Type
          b and Streptococcus pneumoniae Among Infants in Bamako, Mali
          S. O. Sow1, J. Campbell2, M. Tapia2, S. Diallo3, K. Kotloff2, M. Levine2
                                                                                           enhance comprehension. An “ understanding of informed consent” is
                                                                                           administered to volunteers’. Results are provided using descriptive
                                                                                           figures. Results: More than 100 volunteers go through the informed
          1
            Centre pour le Developpement des Vaccins, Bamako, MALI, 2University of         consent process each day for different studies at PSF’s research sites. Ten
          Maryland School of Medicine, Center for Vaccine Development, Baltimore,          are potential volunteers for a protocol establishing normal laboratory
          MD, 3Clinical Bacteriology Laboratory and the Pediatric Service, Gabriel Touré   values for Rwanda as part of preparedness activities for HIV vaccine
          Hospital, Bamako, MALI.                                                          trials. During the first two weeks of that study, 48 volunteers were
                                                                                           screened, 85% were enrolled. Less than 0.05 % was eliminated because
    Background: Immunization with H. influenzae type b (Hib)                               they did not understand the consent. Conclusions: The informed
conjugate is routine in industrialized countries and pneumococcal                          consent is particularly challenging in African research settings. The
conjugate vaccines are increasingly used. In developing countries the                      standardization results in time saving, and prevents subtleties in
paucity of quantitative data on invasive Hib and pneumococcal disease                      language from hindering comprehension.
has impeded decisions about whether to introduce routine
immunization against these infections. Methods: Children age 0-15                          Reference:
years with fever > 39o C or syndromes compatible with invasive                             1. University of Chicago, Institutional Review Board Social and
bacterial disease were eligible. Blood and relevant body fluids (e.g.                         Behavioral Sciences. Policies: Informed Consent. Access on December
cerebrospinal fluid (CSF)) were cultured. Bacteria were identified by                         27th 2004.
standard microbiologic techniques. Results: From June, 2002 to May,                           http://humansubjects.uchicago.edu/sbsirb/manual/consent_policies.s
2004, 3,381 Bamako infants age 0-11 months were admitted to Hôpital                           html
Gabriel Touré. 1,728 infants were eligible and 1,547 (89.5%) were
enrolled. Among these, 185 (11.9%) died. Hib was isolated from 159
infants (10.3%) including 104 positive CSF cultures, 17 infants died
(10.7%). S. pneumoniae was isolated from 117 (7.6%) infants including
85 from CSF, 22 of these died (18.8%). Most infections (148 Hib and
62 S. pneumoniae) occurred in infants age 4-11 months; 17.6% of all
                                                                                           P28       Compatibility of Co-administered 7-valent Pneumococcal
                                                                                                     Conjugate, DTaP.IPV/PRP-T Hib and Hepatitis B Vaccines in
                                                                                                     Infants
admissions in this age group were due to invasive Hib and                                            D. W. Scheifele1, S. Halperin2, B. Smith2, K. Meloff3, D. Duarte-Monteiro3;
pneumococcal infections. All Hib related deaths and 11 of those                                      1
                                                                                                       University of British Columbia, Vancouver, BC, CANADA, 2Dalhousie University,
associated with S. pneumoniae occurred among infants age 4-11 months,                                Halifax, NS, CANADA, 3Wyeth Pharmaceuticals, Toronto, ON, CANADA.
accounting for 35% of all deaths observed among enrollees in this age
group. Conclusions: Hib and pneumococcal infections were major                                 Current immunization schedules for infants recommend
causes of hospitalization and death among infants in Bamako and                            simultaneous administration of several vaccines. This study assessed the
indicate a need to introduce immunization against these infections.                        compatibility of concurrently administered 7-valent pneumococcal
Since most invasive Hib and pneumococcal disease occurs beyond 4                           conjugate (PCV7), hepatitis B (HB) and DTaP.IPV/Hib (P5) vaccines.
months of age, high coverage through routine immunization at 6, 10                         Healthy infants were enrolled at 2 months of age and randomly assigned
and 14 weeks of age should prevent most of these infections.                               (2:1) to receive P5 and HB at 2,4,6 months, with PCV7 given
                                                                                           concurrently or sequentially (at 3,5,7 months). Adverse events were
References:                                                                                monitored for 3 days after each vaccination. Blood was obtained before
1. Campbell JD, Kotloff KL, Sow SO, et al. Invasive Pneumococcal                           dose 1 and after dose 3 to measure antibody responses to each antigen.
   infections among hospitalized children in Bamako, Mali. Pediatr                         376 infants were enrolled and 368 completed the full protocol,
   Infect. Dis. J 2004; 23 (7):642-9.                                                      including 246 concurrent and 122 sequential vaccinees. Responses to
2. Sow S, Diallo S, Campbell J, et al. Burden of Invasive Disease Caused                   PCV7 were unaltered by concurrent P5 and HB vaccinations. Responses
   by Haemophilus influenzae type b in Bamako, Mali: Impetus for                           to P5 were generally unaltered by concurrent PCV7 vaccination except
   Routine Infant Immunization with Conjugate Vaccine. Accepted for                        Hib anti-PRP responses were enhanced (final GMC 1.11 vs 0.64 ug/mL
   publication.                                                                            [concurrent vs sequential], p=0.008). Sequential vaccination increased
                                                                                           responses to diphtheria as a result of repetitive stimulation by toxoid and
                                                                                           CRM197. Responses to HB vaccine were greater with sequential (when


 76
   on Vaccine Research
                           ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
HB and P5 were injected in opposite thighs) than concurrent                                      Comparison of the Safety and Immunogenicity of Simultaneous or
vaccinations ( HB and P5 given adjacent, same thigh) . Concurrent
vaccinations were well tolerated, with no increase in the rate of fever.
                                                                                      P30        Sequential Administration of an Adult Formulation Tdap Vaccine
                                                                                                 and Influenza Vaccine
We conclude that PCV7 and DTaP.IPV/Hib are compatible when                                       S. McNeil1, F. Noya2, M. Dionne3, G. Predy4, W. Meekison5, C. Ojah6,
administered concurrently to infants in opposite thighs. Injecting HB                            S. Ferro7, E. Mills7, J. Langley1, S. Halperin1;
vaccine adjacent to DTaP.IPV/Hib may decrease responses to HB.                                   1
                                                                                                   Dalhousie University, Halifax, NS, CANADA, 2Montreal Children’s Hospital,
“Adjacency” effects on responses warrant further study.                                          Montreal, PQ, CANADA, 3INSPQ, Quebec City, PQ, CANADA, 4Capital-Health,
                                                                                                 Edmonton, AB, CANADA, 5Westcoast Clinical Research, Vancouver, BC,
References:                                                                                      CANADA, 6Saint John Regional Hospital, Saint John, NB, CANADA, 7Sanofi-
1. Halperin SA et al. Safety and immunogenicity of two acellular                                 Pasteur, Toronto, ON, CANADA.
   pertussis vaccines with different pertussis toxoid and FHA content in
   infants 2-6 months old. Scand J Infect Dis 1995;27:279-87                               Background: The annual contact for influenza vaccination provides
2. Heubner RE et al. Immunogenicity after1,2or 3 doses and impact on                  an opportunity to ensure that adults have received other recommended
   the antibody response to co-administered antigens of a nonavalent                  vaccines such as Tdap. Methods: Healthy 19-64-year-olds were
   pneumococcal conjugate vaccine in infants in Soweto, South Africa.                 randomized to concurrent administration of Tdap and influenza vaccine
   Pediatr Infect Dis J 2002;21:1004-7                                                (GroupA) or influenza vaccine followed in 4 to 6 weeks by Tdap
                                                                                      (GroupB). Results: 720 participants were enrolled. No differences were
                                                                                      observed in the rates or severities of injection-site (Tdap-site) erythema,
                                                                                      swelling, or pain. Injection-site pain was the most commonly reported

P29       Research Subject Satisfaction Assessment: a Missing Element of
          “Good Clinical Practices”
          C. LaJeunesse, A. Kallos, K. Marty, M. Mozel, D. W. Scheifele
                                                                                      adverse event (66.6% GroupA v. 60.8% GroupB); most pain was graded
                                                                                      as mild and resolved by Day 3. Seroprotection and seroresponse rates for
                                                                                      all influenza strains were comparable between the 2 groups. For
          Vaccine Evaluation Center, University of British Columbia, Vancouver, BC,   diphtheria and tetanus, seroprotection rates and post-vaccination GMTs
          CANADA.                                                                     were non-inferior in GroupA compared to GroupB. A trend for lower
                                                                                      antibody responses to pertussis antigens PT, FHA, and FIM was
    Regulatory agencies such as Health Canada and the FDA shape                       observed after concomitant administration and, for PRN, this difference
clinical practice for conducting research in humans. Their regulations                met statistical significance. However, GMTs to all antigens in both
are based on Good Clinical Practice Guidelines ( GCP) from the                        groups exceeded levels achieved by infants in pre-licensure, effacy-trials.
International Conference on Harmonization. GCPs require clinical                      Conclusion: While there is a small diminution in antibody response,
research professionals to ensure that subjects’ rights, dignity and safety            concomitant administration of Tdap and influenza vaccine was well-
are respected from the time of recruitment to study completion. While                 tolerated and immunogenic, and may offer practical advantages
most researchers believe that they adhere to accepted guidelines, an                  including convenience, compliance, and cost-savings.
evaluation of their success by study participants is not required. We
developed an assessment tool and anonymously surveyed the                             References:
satisfaction of parents of 698 children as they completed study                       1. De Serres G, Shadmani R, Duval B, et al. Morbidity of pertussis in
participation. The 3 vaccine trials ( 2 sponsored, one grant-funded)                     adolescents and adults. J Infect Dis 2000;182:174-9
included 169 toddlers, 155 pre-kindergarten and 374 grade 6 children,                 2. Gustafsson L, Hallander HO, Olin P, et al. A controlled trial of a
respectively, and involved 1-3 vaccination visits and two venipunctures                  two-component acellular, a five-component acellular, and a whole-cell
per subject. Compliance with survey completion averaged 66% ,                            pertussis vaccine. N Engl J Med 1996. 334(6): 349-55.
ranging from 41% by mail to 98% when done at the final visit. Parents
rated their level of satisfaction with several aspects of the study related
to GCPs using a Likert scale. For example, 438 ( 96.7 %) felt they

                                                                                      P31
understood the study at entry and 433 (95.4%) felt well informed                                 Measurement of Tetanus Antitoxin in Oral Fluid: A Novel Method
during the study. Overall, 94% of parents felt participation was                                 to Evaluate Vaccination Programs
beneficial and 91% would consider participating in a future study. The                           M. D. Tapia1, L. Cuberos1, S. O. Sow2, M. N. Doumbia2, M. Bagayogo2, M.
results indicate that our team provided an explicit, respectful and safe                         Pasetti1, K. Kotloff1, M. Levine1
experience for participants, as intended. We believe that end of study                           1
                                                                                                   University of Maryland School of Medicine, Baltimore, MD, 2Centre pour le
evaluations from subjects should be a standard practice, added to GCP                            Developpement des Vaccins - Mali, Bamako, MALI.
codes.
                                                                                          Background: Oral fluid has been used in surveys and detection of
References:                                                                           responses to vaccination. Measurement of tetanus antitoxin may serve as
1. Reynolds SM ORI findings of scientific misconduct in clinical trials               an objective means to assess the effectiveness of vaccination programs. A
   and publicly funded research, 1992-2002. Clinical Trials                           survey was conducted to determine whether IgG tetanus antitoxin could
   2004;1:509-516                                                                     be measured in oral fluid. Methods: Serum and oral fluid were collected
2. Knatterrud GL et al Guidelines for quality assurance in multicenter                from infants, toddlers and adults (males without history of vaccination
   trials: a position paper. Control Clin Trials 1998;19:477-93                       against tetanus), residing in rural Mali. IgG tetanus antitoxin was
                                                                                      measured by standard enzyme linked immunosorbent assay in serum
                                                                                      (S-ELISA) and oral fluid (OF-ELISA). Results: 215 pairs of serum and
                                                                                      oral fluid samples were collected. There was approximately 10-fold less
                                                                                      IgG tetanus antitoxin measured by OF-ELISA than S-ELISA. There was
                                                                                                                                                                (continued)


                                                                                                                                                                         77
         Eighth Annual Conference
                             ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
an excellent correlation between anti-tetanus IgG measured by S-ELISA                            A Novel Combination DNA and Inactivated Rabies Virus Vaccine
and OF-ELISA (r=0.83, p < 0.001). OF-ELISA was 82% sensitive and
100% specific compared to S-ELISA for the detection of protective
                                                                                       P33       P. N. Rangarajan1, V. A. Srinivasan2
                                                                                                 1
                                                                                                   Indian Institute of Science, Bangalore, INDIA, 2Indian Immunologicals Limited,
titers (0.001 IU/ml in oral fluid corresponded with 0.01 IU/ml in                                Hyderabad, INDIA.
serum). Infants and toddlers who had received 1, 2, or 3 doses of
diphtheria-tetanus-pertussis (DTP) vaccine had increasing geometric                        Background: The high cost of production of cell culture-derived
mean concentrations of tetanus IgG detected by S-ELISA (1.3, 2.8 and                   rabies vaccines render them unaffordable to a sizeable population in the
3.3 IU/ml, respectively) and OF-ELISA (0.006, 0.0171, and 0.0175                       developing countries where rabies remains a serious public health
IU/ml). Conclusions: Levels of IgG tetanus antitoxin in oral fluid                     problem. DNA vaccines can be produced at a low cost and are storable
correlate well with levels in serum. OF-ELISA offers a non-invasive                    at room temperature and thus is an ideal choice for rabies eradication
objective tool to supplement information collected in coverage surveys.                programmes in developing countries. Methods: A novel combination
                                                                                       rabies vaccine (CRV) formulation containing an eukaryotic expression
References:                                                                            plasmid encoding rabies virus surface glycoprotein and a small quantity
1. Morris-Cunnington MC, Edmunds WJ, Miller E, Brown DW. A                             of cell culture-derived inactivated rabies virus was developed. The
   population-based seroprevalence study of hepatitis A virus using oral               potency of CRV was examined in mice and cattle by examining the
   fluid in England and Wales. Am J Epidemiol. 2004 Apr                                rabies virus neutralizing antibody titres as well as protection against
   15;159(8):786-94.                                                                   virus challenge. Results: Mice immunized with CRV develop higher
2. Zhang Q, Lakshman R, Burkinshaw R, et al. Primary and booster                       levels of rabies virus neutralizing antibodies (RVNA) than those
   mucosal immune responses to meningococcal group A and C                             immunized with DNA Rabies vaccine (DRV) and are completely
   conjugate and polysaccharide vaccines administered to university                    protected against peripheral as well as intracerebral rabies virus
   students in the United Kingdom. Infect Immun. 2001                                  challenge. The quantity of inactivated rabies virus vaccine required for
   Jul;69(7):4337-4                                                                    enhancing the potency of DRV can be 625 fold lower than that of a
                                                                                       standard dose of inactivated rabies virus vaccine. CRV induces higher
                                                                                       levels of RVNA than DRV in cattle as well. Conclusions:
                                                                                       Coinoculation of DNA vaccine and a low dose of inactivated virus
P32       Studies on a Live Oral Attenuated Cholera Vaccine, Peru-15 in
          Bangladesh
          F. Qadri1, M. I. Chowdhury1, M. A. Salam1, S. M. Faruque1, T. Ahmed1,
                                                                                       vaccine can be developed into a novel cost-effective vaccination strategy
                                                                                       for combating rabies in particular and infectious diseases in general.
          Y. A. Begum1, A. Saha1, L. V. Seidlein2, R. F. Breiman1, J. J. Mekalanos3,
          J. D. Clemens2, K. P. Killeen4, D. A. Sack1                                  Reference:
          1
            ICDDR,B: Centre for Health and Population Research, Dhaka, BANGLADESH,     1. Biswas S, Reddy, GS, Srinivasan VA, Rangarajan PN. Pre-exposure
          2
            International Vaccine Institute, Seoul, DEMOCRATIC PEOPLE’S REPUBLIC OF       efficacy of a novel combination DNA and inactivated rabies virus
          KOREA, 3Harvard Medical School, Boston, MA, 4AVANT Immunotherapeutics,          vaccine. Hum. Gene Ther. 2001;12:1917-1922
          Needham, MA.

     Background: The objective was to facilitate the development of a new
live oral cholera vaccine that is safe, immunogenic and protective against
cholera caused by the V. cholerae O1 El Tor biotype, the pandemic strain
now causing cholera. Progress has been made on Peru-15a, derived from
                                                                                       P34       Minicircle DNA Immobilized in Bacterial Ghost: A Novel Non-living
                                                                                                 Bacterial DNA-vaccine Carrier System
                                                                                                 C. Azimpour Tabrizi1, W. Jechlinger2, P. Becker3, T. Ebensen3, C. Guzman3,
a V. cholerae O1 El Tor strain which was previously demonstrated to be                           W. Lubitz1
immunogenicb and efficacious against O1 El Tor cholera in clinical trials.                       1
                                                                                                   Microbiology and Genetic, Vienna, AUSTRIA, 2Inst. Bacteriology, Mycology and
Methods: A randomized double-blind placebo controlled study was                                  Hygiene, Vienna, AUSTRIA, 3German Research Centre for Biotechnology,
carried out by the ICDDR,B in Dhaka in collaboration with                                        Braunschweig, GERMANY.
International Vaccine Institute and AVANT Immunotherapeutics Inc.
The study was carried out in Dhaka in adults (n=70) and children                           Despite the exponential rate of discovery of DNA vaccines resulting
(n=120) using Peru-15 at a dose of 2x108CFU. Results: Peru-15 was                      from modern molecular biology, the lack of the effective delivery
found to be safe no significant increase in symptoms attributed to the                 technology is a major limiting factor in their applications. We had
vaccine.Over 75% seroconversion rates were documented in vibriocidal                   recently reported a new platform technology based on the
antibodies with _ 256-fold increases in titers over baseline. It also                  immobilization of plasmid DNA in the inner membrane of bacterial
stimulated antibody responses to lipopolysaccharide.The strain remained                ghosts (SIP)1. Furthermore, this system was combined with an in vivo
unchanged in genetic and phenotypic properties on excretion.                           site-specific recombination technology, in which an origin plasmid
Conclusions: Based on these encouraging results, the study has                         divides into a minicircle and a miniplasmid. The replicative
progressed to the infant phase(9-23m).We hope the information                          miniplasmid containing the origin of replication and the antibiotic
obtained from these studies will be useful in planning future studies with             resistance gene was lost during the bacterial ghost production2, whereas
it in Bangladesh.                                                                      the minicircle DNA containing only the eukaryotic expression cassette
                                                                                       was retained in the bacterial ghosts via the SIP technology. In vivo
References:                                                                            studies showed that immunization of C57Bl6 mice with bacterial ghosts
1. Kenner JR, Coster TS, Taylor DN, et al. Peru-15, an improved live                   harbouring immobilized minicircle encoding ovalbumin, results in
   attenuated oral vaccine candidate for Vibrio cholerae O1. J Infect Dis              humoral and cellular immune responses against the target antigen.
   1995;172:1126-9                                                                     Immune responses stimulated by ghost-mediated DNA delivery were
2. Sack DA, Sack RB, Shimko J, et al. Evaluation of Peru-15, a new live                evaluated by ELISA and ELISPOT assay to show the capacity of T-cells
   oral vaccine for cholera, in volunteers. J Infect Dis 1997;176:201-5                to produce Antibodies and cytokines, like IL-2, IL-4 and IFN-_. The

 78
   on Vaccine Research
                            ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
significant amount of the IgG and IL-4 in the immunized mice showed                                   Infanrix™-IPV-Hib (GSK) is Safe and Immunogenic Compared to
the bias of the immune response toward Th2 responses and proliferation
of the B-cells. In addition, the efficient IFN-_ production indicated that
                                                                                            P36       Pentacel™ (Sanofi Pasteur) as a 4th Dose in 15-20 Month Olds
                                                                                                      S. A. Halperin1, B. Tapiero2, B. Law3, B. Duval4, F. Diaz-Mitoma5, D. Elrick6;
the bacterial ghosts as DNA delivery vehicles are also able to effectively                            1
                                                                                                        Pediatrics, Dalhousie University, Halifax, NS, CANADA, 2Pediatrics, Ste Justine
stimulate the cellular arm of the immune response.                                                    Hospital, University of Montreal, Montreal, PQ, CANADA, 3Pediatrics,
                                                                                                      University of Manitoba, Winnipeg, MB, CANADA, 4Institut National de Santé
References:                                                                                           Publique, Quebec City, PQ, CANADA, 5Pediatrics, Children’s Hospital of Eastern
1. Mayrhofer P, Azimpour T.C, Walcher P, Haidinger W, Jechlinger W,                                   Ontario, Ottawa, ON, CANADA, 6GlaxoSmithKline, Inc, Mississauga, ON,
   Lubitz W. Immobilization of plasmid DNA in bacterial ghosts. J                                     CANADA.
   Control release 2004; available online.
2. Azimpour T.C, Walcher P, Mayr U.B, Stiedl T, Binder M, McGrath                               Background: In Canada, children are immunized using Pentacel™.
   J.F, Lubitz W. Bacterial ghosts-Biological particles as delivery systems                 GSK also produces a pentavalent DTPa-IPV-Hib (Infanrix™-IPV-Hib).
   for antigens, nucleic acids and drugs. Curr Opinn Biotech 2004,                          Methods: 15-20 month olds previously immunized with 3 doses of
   15(6): 530-537.                                                                          Pentacel™ were randomised to receive 1 dose of Pentacel™ or
                                                                                            Infanrix™-IPV-Hib. Results: 433 participants were enrolled. Redness
                                                                                            >20 mm was reported after 11.5% of Pentacel™ and 5.6% of
                                                                                            Infanrix™-IPV-Hib (p=.038). Injection site pain was more common

P35       Multiple DNA Vaccine Plasmids Protect Mice from Acute
          Pulmonary Infection of Pseudomonas aeruginosa
          S. Saha1, F. Takeshita1, S. Sasaki1, T. Matsuda1, T. Matsumoto2, K. Yamaguchi2,
                                                                                            after Pentacel™ (52.1%) than Infanrix™-IPV-Hib (39.4%; p=.009).
                                                                                            Moderate or greater drowsiness was more common after Pentacel™
                                                                                            (13.8%) than Infanrix™-IPV-Hib (7.4%; p=.042). The proportion of
          K. Okuda1                                                                         participants that were seroprotected and GMTs were similar for
          1
            Yokohama City University Graduate School of Medicine, Yokohama, JAPAN,          diphtheria, tetanus, and polio. Similar proportions responded to
          2
            Toho University School of Medicine, Tokyo, JAPAN.                               pertussis antigens; GMTs were higher in the Infanrix™-IPV-Hib than
                                                                                            the Pentacel™ group against pertussis toxoid (88.5 vs. 65.6 EU/mL),
    We studied the immunogenicity of three DNA vaccine plasmids                             filamentous hemagglutinin (207.3 vs. 132.1) and pertactin (251.9 vs.
encoding P. aeruginosa antigens, a fusion protein of outer membrane                         166.9). The proportion seroprotected against Hib was similar (99.5%
protein F and outer membrane protein I (OprF/I), type III translocation                     vs. 98.4%); GMTs were higher in the Pentacel™ (29 _g/mL) than the
protein (PcrV), and pilin protein (PilA). BALB/c mice were immunized                        Infanrix™-IPV-Hib (19 _g/mL) group. Conclusion: A booster dose of
twice with single (OprF/I, PcrV, or PilA alone) or mixture of three                         Infanrix™-IPV-Hib after 3 priming doses of Pentacel™ is safe and
plasmids (OprF/I+PcrV+PilA) by using intramuscular electroporation                          immunogenic in 15-20 month old infants. Infanrix™-IPV-Hib can be
(imEP) technology. Two weeks after 2nd immunization, mice were                              used as an alternative to Pentacel™ for the 4th dose in infants primed
administered intarnasally with P. aeruginosa D4. The higher number of                       with 3 doses of Pentacel™.
the lung bacteria was recovered in groups of mice vaccinated with each
single plasmid than OprF/I+PcrV+PilA group. Bacteremia was present                          References:
in all groups except OprF/I+PcrV+PilA group. The expression of MIP-2,                       1. Halperin SA, Davies HD, Barreto L, et al. Safety and
TNF_, and IFN_ mRNA in broncho alveolar lavage cells were                                      immunogenicity of two inactivated poliovirus vaccines in
significantly upregulated in OprF/I+PcrV+PilA group. Finally >10 d                             combination with an acellular pertussis vaccine and diphtheria and
after bacteria challenge, the superior survival rate was observed in                           tetanus toxoids in seventeen month old infants. J Pediatr.
OprF/I+PcrV+PilA group compared with that in the group of mice                                 1997;130:525-3
vaccinated with each single plasmid.                                                        2. Halperin SA, King J, Law B, Mills E, Willems P. Safety and
The method of vaccine delivery was also examined. Multiple plasmid                             immunogenicity of Haemophilus influenzae-tetanus toxoid conjugate
DNA vaccine by imEP method provided potent protection against P.                               vaccine given separately or in combination with a three-component
aeruginosa challenge over that by gene gun method although serum IgG                           acellular pertussisvaccine...Clin Infect Dis. 1999;28:995-1
levels were comparably induced by both methods.
In conclusion, multiple DNA vaccine targeting three different
components, OprF/I, PcrV, and PilA, delivered by imEP elicited the
strongest protection ability. These data would assist the development of                              Immunization with Recombinant Adenovirus Synthesizing
P. aeruginosa vaccine for pulmonary infections.                                             P37       Secretory Form of Japanese Encephalitis Virus Envelope Protein
                                                                                                      Protects Adenovirus-Exposed Mice Against Lethal Encephalitis
References:                                                                                           S. Vrati
1. Sawa T, Yahr TL, Ohara M, Kurahashi K, Gropper MA, Wiener-                                         National Institute of Immunology, New Delhi, INDIA.
   Kronish JP, and Frank DW. Active and passive immunization with the
   Pseudomonas V antigen protects against type III intoxication and                             Background: We have previously shown that immunization with a
   lung injury. Nature Medicine 1999; 5:392-398                                             plasmid DNA synthesizing pre-Membrane (prM) and envelope (E)
2. Grifantini R, Finco O, Bartolini E, Draghi M, Giudice GD, Kocken                         proteins of Japanese encephalitis virus (JEV) provided partial protection
   C, Thomas A, Abrignani S and Grandi G. Multi plasmid DNA                                 to mice against lethal JEV challenge [1]. An improved delivery of DNA
   vaccination avoids antigenic competition and enhances                                    encoding these two proteins using recombinant adenovirus (RAd) is
   immunogenicity of a poorly immunogenic plasmid. Eur. J. Immunol                          likely to induce enhanced immune response against JEV [2]. Methods:
   1998; 28:1                                                                               Replication-defective RAds were constructed that synthesized the prM
                                                                                            and E proteins of JEV. Potential of these recombinants for vaccination
                                                                                                                                                                        (continued)


                                                                                                                                                                                  79
          Eighth Annual Conference
                            ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
against JEV was examined in mice by studying their immunogenicity               References:
and protective efficacy. Results: Recombinant virus RAdEa,                      1. Koutsky LA, Ault KA, Wheeler CM, et al. A controlled trial of a
synthesizing the membrane-anchored E protein, replicated poorly in                 human papillomavirus type 16 vaccine. N Eng J Med 2002;
HEK 293A cells and synthesized lower amounts of E protein than                     347(21):1645-1651.
RAdEs synthesizing the secretory E protein. Oral immunization of mice           2. Suzich JA, Ghim SJ, Palmer-Hill FJ, et al. Systemic immunization
with RAds generated low titers of anti-JEV antibodies with little JEV              with papillomavirus L1 protein completely prevents the
neutralizing activity. Intra-muscular (IM) immunization of mice with               development of viral mucosal papillomas. Proc Natl Acad Sci USA
both RAds generated high titers of anti-JEV antibodies. Interestingly,             1995; 92: 11553-11557.
RAdEa induced only low titers of JEV neutralizing antibodies, whereas
these were significantly higher in case of RAdEs immunization. Naïve
mice immunized IM with RAdEs showed complete protection against
lethal JEV challenge. In order to study the effect of the pre-existing
Adenovirus 5 (Ad5) immunity on the outcome of RAdEs immunization,
mice were exposed to Ad5 through IM or intra-nasal (IN) routes before
                                                                                P39       Construction of Live Attenuated Shigella Vaccine Candidates
                                                                                          using Recombineering
                                                                                          R. Ranallo, S. Barnoy, S. Thakkar, M. Venkatesan
immunization with RAdEs. Mice exposed to Ad5 through the IN route,                        Enteric Infections, WRAIR, Silver Spring, MD.
when immunized IM with RAdEs, or those exposed to Ad5 through the
IM route, when immunized IN with RAdEs, showed complete                             Live attenuated Shigella vaccines have shown promise in inducing
protection against lethal JEV challenge.Conclusions: High levels of             protective immune responses and as carriers of heterologous antigens
protective immunity induced by RAdEs in Ad5-exposed mice by the IM              from other mucosal pathogens. In the past, construction of Shigella
immunization point to its potential as a candidate JEV vaccine.                 vaccine strains has relied on classical allelic exchange systems to transfer
                                                                                alleles from one strain to another. These systems require extensive in
References:                                                                     vitro engineering of long homologous sequences to create recombinant
1. Kaur R, Sachdeva G, Vrati S. Plasmid DNA immunization against                replication-defective plasmids or phage. Alternatively, the Lambda red
   Japanese Encephalitis Virus: immunogenicity of membrane-anchored             recombination system from bacteriophage Lambda facilitates
   and secretory envelope protein. J Infect Dis 2002; 185:1-12.                 recombination with as little as 50bp of homologous DNA. However,
2. Casimiro DR, Chen L, et al. Comparative immunogenicity in rhesus             until recently this system has been restricted for use in E. coli. The
   monkeys of DNA plasmid, recombinant vaccinia virus, and                      process, referred to as recombineering, typically uses an inducible red-
   replication-defective adenovirus vectors expressing a human                  gam operon on a temperature-sensitive plasmid and optimal
   immunodeficiency virus type 1 gag gene. J Virol 2003; 77:6305-               transformation conditions to integrate linear antibiotic resistance
   6313.                                                                        cassettes into bacterial genomes. Recent advances in the Lambda red
                                                                                recombination system have enabled modification of genomic DNA
                                                                                from bacterial pathogens such Salmonella typhimurium, EPEC, or
                                                                                EHEC using short regions of homology thus eliminating the tedious in
P38        A Novel Live Adenovirus Vaccine Vector Prototype:
           High-level Antigen Production from the Adenoviral Major Late
           Transcriptional Unit
                                                                                vitro steps associated with plasmid or phage construction. We have used
                                                                                these advances in Lambda red recombineering to delete virulence-
                                                                                associated genes from Shigella creating a number of isogenic strains
           M. G. Berg1, B. Falgout2, G. W. Ketner1
                                                                                from multiple Shigella species. These strains have been characterized for
           1
             Molecular Microbiology and Immunology, Johns Hopkins University,
                                                                                attenuation using both in vivo and in vitro assays. Based on this data,
           Baltimore, MD, 2Cber, Food & Drug Administration, Bethesda, MD.
                                                                                prototypic Shigella vaccine strains containing multiple deletions in
                                                                                virulence-associated genes have been created. Thus through protocol
    Safe, effective, orally-delivered live adenovirus vaccines (Ad4 & Ad7)
                                                                                optimization and newly available plasmids, we have used Lambda red
have been used for three decades and recombinant derivatives of these
                                                                                recombineering to rapidly construct several potential Shigella vaccine
may prove a novel approach to vaccine development or an economical
                                                                                strains with up to four precise genetic lesions.
alternative to some current vaccines. We sought to design a replicating
vector system that is inexpensive, produces high antigen levels, and
                                                                                References:
protects in a single dose. As a proof of principle, we constructed a series
                                                                                1. Murphy, K.C. and K. G. Campellone. Lambda Red-mediated
of novel Ad5 recombinants that express the major capsid protein (L1) of
                                                                                   recombinogenic engineering of enterhemorrhagic and
canine oral papillomavirus (COPV), a model for mucosal human
                                                                                   enterpathogenic E. coli. BMC Mol Biol. 2003 Dec 13;4(1):11.
papillomavirus (HPV) infection. Our recombinants incorporate COPV
                                                                                2. Court D.L., Sawitzke J.A., and L.C. Thomason. Genetic
L1 into adenovirus late region 5 (Ad L5) so that it is expressed as a
                                                                                   Engineering Using Homologous Recombination. Annu. Rev. Genet.
member of the adenoviral MLTU. COPV L1 production is influenced
                                                                                   2002. 36:361-88.
by Ad L5 gene order, the specific mRNA processing signals associated
with COPV L1, and the state of a putative splicing inhibitor in the
COPV L1 gene. Recombinant COPV L1 protein assembles into VLPs
and also reacts with an antibody specific for conformational epitopes on
native COPV L1 protein that correlate with protection in vivo. We have
now built similar prototype vaccines intended for the prevention of
cervical cancer as well as dengue fever. These express L1 from the high
risk serotype, HPV16, or the Dengue1 antigens, pre-M and E. Our data
illustrates the versatility of this expression system and the possibility for
the construction of recombinant adenovirus vaccines against a variety of
diseases.

 80
   on Vaccine Research
                           ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
          Oral Immunization of Dogs with Baits Containing the                            Reference:
P40       Recombinant Rabies Virus Glycoprotein/ Nucleoprotein-canine
          Adenovirus Type 2
                                                                                         1. Bystrick_ S., Paulovi_ová E., Machová E. Candida albicans mannan-
                                                                                            protein conjugate as vaccine candidate. Immun. Letters. 2003; 85:
          R. Hu, S. Zhang, H. li                                                            251-255
          Veterinary Institute, Academy of Military Medical Science, Changchun, CHINA.

    Background: Human rabies is mostly caused by bite of rabid dogs.
Immunization of dogs in countryside with currently commercial rabies
vaccine is laborious and costly. To develop an oral rabies vaccine effective             P42       A Novel Subunit Vaccine Protects Mice Against Systemic Disease
                                                                                                   and Intestinal Colonization by Salmonella enterica
                                                                                                   L. Wonderling1, D. Straub2, D. Emery2
and easily used for dogs, we developed two recombinant canine
adenoviruses type-2 expressing rabies virus glycoprotein and                                       1
                                                                                                     Syntiron, Saint Paul, MN, 2Epitopix, Willmar, MN.
nucleoprotein, respectively. Methods: The recombinant viruses were
constructed by cloning the rabies virus glycoprotein and nucleoprotein                       Salmonella enterica is a leading cause of bacterial foodborne diseases
expression cassette into the deleted E3 region of canine adenovirus type-2,              world wide. In response to the lack of immunoprophylactic treatment
and were packaged, propagated and produced on MDCK. The                                  and the need to identify potential vaccine targets for preventing
recombinant vaccine baits, which are made by injecting 3_108.5 TCID50                    infections by Salmonella, our research efforts focused on the
recombinant viruses into tampon enwrapped by fat with a T-shape metal                    development of a novel subunit vaccine for controlling Salmonella. Iron
frame attached, were fed to dogs and tested for safety and efficacy. Results:            uptake proteins have been identified as potent immunogens in other
Two weeks after initial oral administration, 50% of the immunized dogs                   gram-negative species. Many of these proteins are large, surface-exposed,
developed antibodies against rabies virus and the vector adenovirus. After               and expressed during infection of a mammalian host. S. enterica also
booster with an interval of two weeks, 85% of the immunized dogs                         expresses a number of iron uptake proteins, and in the present
became seroconverted. The neutralizing antibody, tested by mouse                         investigation we sought to determine if these proteins may constitute
intracerebral neutralization, showed that 5_22 diluted serum could                       effective vaccine antigens. Membrane proteins produced by S. enterica
neutralize 300 LD50 CVS-240 intracerebral infection. The immunized                       under iron-limiting conditions were formulated into a vaccine and
dogs showed no clinical and pathogenic changes after the inoculation.                    tested for efficacy in the murine host. When compared to unvaccinated
Conclusion: It has demonstrated that the recombinant rabies virus                        mice, the intraperitoneal (i.p.) administration of the multi-protein
glycoprotein and nucleoprotein-canine adenovirus vaccine baits are of oral               vaccine to mice significantly (p≤ 0.035) reduced the fecal shedding of
safeness, effectiveness and ease for rabies prevention in dogs.                          Salmonella following an oral dose of the pathogen. In addition, the
                                                                                         vaccine’s effects on systemic challenge were tested by i.p. administration
Reference:                                                                               of vaccine and a subsequent i.p. challenge. The results show significantly
1. Xiang ZQ, Gao GP, Reyes-Sandoval A, et al. Oral vaccination of mice                   (p= 2.06 x 10-13) fewer deaths in the group of mice administered the
   with adenoviral vectors is not impaired by preexisting immunity to                    vaccine preparation as compared with unvaccinated mice. Taken
   vaccine carrier. J Virol 2003; 77:10780-10789.                                        together, these results suggest that one or more proteins present in the
                                                                                         membranes of S. enterica grown under iron-limiting conditions provide
                                                                                         protection against both an oral and systemic challenge of S. enterica.
                                                                                         Ongoing investigations seek to identify the proteins responsible for
                                                                                         protection against S. enterica.
P41       Immunological Properties of Conjugates Prepared from Pathogenic
          Candida Surface Antigens - Potential Vaccines
          S. Bystricky                                                                   References:
          Institute of Chemistry SAV, Bratislava, SLOVAKIA.                              1. Mead, P.S., Slutsker, L., Dietz, V., McCraig, L.F., Bresee, J.S.,
                                                                                            Shapiro, C., Griffin, P.M., and Tauxe, R.V. 1999. Food-related illness
    Infections caused by opportunistic pathogens, namely by Candida                         and death in the United States. Emerg. Infect. Dis. 5:607-625.
species occur increasingly because of the wide use of broad-spectrum                     2. Bjarnason, J., Southward, C.M., and Surette, M.G. 2003. Genomic
antibiotics, chemotherapy and immunosuppressing drugs in the recent                         profiling of iron-responsive genes in Salmonella enterica serovar
years. The systemic diseases caused by pathogenic yeasts lead to life-                      Typhimurium by hihg-throughput screening of a random promoter
threatening conditions in immunocompromised individuals, elderly                            library. J. Bacteriol. 185:4973-7982.
people and infants. There is no effective licenced vaccine yet.
    In our continuing conjugate studies1,2, newly prepared yeast surface
mannan - protein conjugates were used to immunize experimental
rabbits. Induction of specific humoral and celullar immune response was
monitored. Quantitative determination of IgG and IgM by ELISA and                        P43       Partial Protection of Mice after DNA Vaccination Against
                                                                                                   Staphylococcus aureus Infection
                                                                                                   M. C. Gaudreau1, P. Lacasse2, B. G. Talbot1
flow-cytometry of CD4, CD8, CD19, CD25 and CD11b expression on
lymphocytes and granulocytes was performed during whole multiple
                                                                                                   1
                                                                                                     Biologie, University of Sherbrooke, Sherbrooke, PQ, CANADA,
immunizations experiment.
                                                                                                   2
                                                                                                     Agriculture and Agri-Food Canada, Lennoxville, PQ, CANADA.
    Conjugates elicited higher immune response, (especially after first
immunization) than mannan antigen alone or killed whole cells.                               Staphylococcus aureus is an opportunistic human and animal
According to our results we can say, that novel mannan-protein                           pathogen which can cause clinical manifestations ranging from mild
conjugates reflect T-cell dependent character of immunogens with                         skin infections to endocarditis, mastitis, septic arthritis and septicaemia.
evident induction of long-term memory functionality.                                     Our previous work demonstrated that the duration of Staphylococcus
    The yeast mannan conjugate synthesized by this scheme can be                         aureus mastitis in dairy cows could be reduced by immunization with
considered as a vaccine candidate for clinical evaluation.                                                                                                    (continued)


                                                                                                                                                                     81
          Eighth Annual Conference
                             ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
plasmid that expressed bacterial adhesion proteins. The present report               antibodies, (2) expanded fraction of the IgG2a anti-preS1, (3) decreased
describes the murine immune response and its effects on bacterial                    anti-HBc response, and (4) switched cytokine production to the IFN- _
challenge after immunization with genetic vaccines containing up to                  and IL-2 synthesis, which is a sign of induction of the CTL response.
three genes implicated in Staphylococcus aureus adhesion.
    Mice were immunized three times with 100 ug of pCI-based                         References:
(Invitrogen) plasmid DNA. Antibody titers were determined by ELISA.                  1. Song MK, Lee SW, Suh YS, et al. Enhancement of immunoglobulin
Cytokine analysis and cell proliferation assays were carried out by FACS                G2a and cytotoxic T-lymphocyte responses by a booster
analysis. Mice were challenged by I.V. infection with either a human                    Immunization with recombinant Hepatitis C Virus E2 protein in E2
isolate of Staphylococcus aureus or with a less virulent laboratory strain.             DNA-Primed Mice. J Virol 2000;74:2920-2925
    Antibody titers (primarily IgG2a) of up to 20,000 were produced                  2. Pumpens P, Grens E. HBV core particles as a carrier for Bcell/Tcell
against all antigens. Pre-incubation of the bacteria with immune serum                  epitopes. Intervirology 2001;44:98-114
considerably increased in vitro phagocytosis (p 0.01). FACScan analysis
demonstrated little antigen-induced lymphocyte proliferation but a
strong stimulation of IFN_ compared to IL-4 production. Non-
vaccinated mice infected with a virulent bacterial strain died within 4
days, whereas the multigene vaccinated animals showed no signs of
infection until 10 days post-infection. Similarly, only non-vaccinated
                                                                                     P45       Genetic Polymorphism and Positive Selection in a ‘Concealed’ Gut
                                                                                               Potential Vaccine Antigen from Rhipicephalus appendiculatus.
                                                                                               L. M. Kamau1, R. Skilton2, T. Musoke2, D. Wasawo2, J. Rowlands2, R. Bishop2
mice infected with the low virulence strain showed signs of septic or                          1
                                                                                                 Kenyatta University & International Livestock Research Institute (ILRI),
reactive arthritis                                                                             Nairobi, KENYA, 2International Livestock Research Institute (ILRI), Nairobi,
    The results suggest that nucleic acid vaccination against adhesion                         KENYA.
proteins can produce a protective response against Staphylococcus aureus
infection.                                                                               Boophilus microplus Bm86 commercial vaccines control Boophilus
                                                                                     decoloratus and B. annulatus from different parts of the world. They
References:                                                                          showed potential for control of Hyalomma anatolicum anatolicum and
1. Shkreta l., Talbot B.G., Diarra M.S., Lacasse P., Immune responses to             H. dromedarii but insufficient cattle protection against Rhipicephalus
   a DNA/protein vaccination strategy against Staphylococcus aureus                  appendiculatus, an important livestock tick in sub-saharan Africa. In this
   induced mastitis in dairy cows. Vaccine 2004; 23, 114-126                         study, polymorphism in the Bm86 homolog in R. appendiculatus isolated
2. Brouillette E., Lacasse P., Shkreta, L., Grondin G., Fournier S.,                 from four Kenyan field populations and a laboratory stock was
   Bélanger J., Diarra M., Talbot B.G. DNA immunization against                      characterized in view of developing an effective vaccine against this tick.
   Clumping factor A (ClfA) of Staphylococcus aureus. Vaccine 2002;                      An estimated 2 Kb cDNA encoding Bm86 homologue in
   20(17-18) 2348-57                                                                 Rhipicephalus appendiculatus, Ra86(Muguga) was isolated from a cDNA
                                                                                     library constructed using cDNA synthesized from gut RNA extracted
                                                                                     from Rhipicephalus appendiculatus Muguga Laboratory strain. Nine full-
                                                                                     length, including predicted signal peptide and membrane anchor and 10
                                                                                     truncated sequences were analyzed. Two allele types were demonstrated;
P44       Strong B- and T-cell response After Protein, DNA, and DNA
          Prime/Protein Boost Immunisation with HBV Cores Carrying
          HBV PreS1 Sequences
                                                                                     a non-deletion type, potentially encoding 693 amino acids (aa) and a
                                                                                     deletion 4-type (654 aa). Five of 19 (26%) sequences were deletion 4-
          D. Skrastina, I. Sominskaya                                                type and the remaining 74% were non-deletion type. The 40 amino
          Protein Engineering, Biomedical Research and Study Centre, University of   acids deletion near C terminal and 129 (20%) amino acid substitutions
          Latvia, Riga, LATVIA.                                                      from single nucleotide polymorphisms (SNPs) differentiated the two
                                                                                     proteins. Combining Ra86(Muguga) and field isolates, additional
    Hepatitis B virus (HBV) nucleocapsid, or core (HBc) particle,                    deletions (39-48 aa), designated 1, 2, 3 and 4, and the non-deletion type
immunologically defined as Hepatitis B core antigen (HBcAg) gave first               resulted in 5 size types. Non-deletion type was isolated only from
onset to an idea of universal, self-assembling, non-infectious carriers for          Ra86(Muguga) while deletions 1, 2 and 3 were isolated from the field.
foreign epitopes. The major immunodominant region (MIR) of HBc (aa                   Deletion 4-type isolated from the field and laboratory would be the
76-81) is accepted as a target site of choice for insertion of foreign               appropriate vaccine candidate. The polymorphism was due to positive
epitopes. We have chosen the preS1 sequences of different length,                    selection, shown by selective neutrality and neutral evolution tests, and
containing the aa 20-47 region, which are able to elicit HBV-                        was associated with antigenic or another role of the concealed antigen.
neutralising and protective antibodies, as model epitopes for such                   WINA window analysis revealed mutation hot spots scattered over the
insertions. We compared induction of specific B- and T-cell responses                molecule.
after protein, DNA, and DNA prime/protein boost immunisation into
Balb/c mice using ELISA and T-cell proliferation tests. We found that                References:
deletions within the MIR of the full- length HBc, and of the C-                      1. de Vos S, Zeinstra L, Taoufik O, Willadsen P, Jongejan F. Evidence for
terminally truncated HBcAg decrease anti-HBc and increase anti-preS1                    the utility of the Bm86 antigen from Boophilus microplus in
antibody response. The preS1 fragments insertions correspond to the                     vaccination against other tick species. Exp Appl Acarol 2001;
11-60 aa, as well as preS1 11-60 aa plus 89-119 aa into the MIR with                    25(3):245-261
accompanying deletions increase anti-preS1, but decrease anti-HBc                    2. Rand KN, Moore T, Sriskantha A, Spring K, Tellam R, Willadsen P,
antibody response. Three injections of 50 µg of plasmid DNA into M                      et al. Cloning and expression of a protective antigen from the cattle
Tibialis anterior of Balb/c mice induced a high-titered anti-preS1                      tick Boophilus microplus. Proc Natl Acad Sci U S A 1989;
antibodies as documented 7-13 weeks after immunisation. DNA                             86(24):9657-9661
prime/protein boost immunisation (1) enhanced titer of anti-preS1


 82
   on Vaccine Research
                             ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
          A Recombinant 63-kilodalton Form of Bacillus anthracis                              Interestingly, these IgG antibodies are specific to rLmSIR2, consisting
P46       Protective Antigen Produced in the Yeast Saccharomyces
          cerevisiae Provides Protection in two Inhalational Challenge
                                                                                              of a mixed IgG1/IgG2a isotype profile and have minimum reactivity
                                                                                              against other heterologous antigens. Taken together, our data suggest
          Models of Anthrax Infection                                                         that LmSIR2, through direct or indirect action towards B cells, induces
          R. W. Hepler1, R. Kelly1, T. B. McNeely1, H. Fan1, M. C. Losada1, H. A.             a specific immune response.
          George1,
          A. Woods1, L. D. Cope1, A. Bansal1, J. C. Cook1, G. Zang1, S. L. Cohen1, X. Wei1,   References:
          P. M. Keller1, E. K. Leffel2, J. G. Joyce1, M. L. M. Pitt2, L. D. Schultz1,         1. Zemzoumi K., Sereno D., François C., Guilvard E., Lemestre J.L.,
          K. U. Jansen1, M. Kurtz1                                                               Ouaissi A. (1998). Leishmania major: cell type dependent
          1
            Merck Research Labs, West Point, PA, 2US Army Medical Research Institute of          distribution of a 43 KDa antigen related to silent information
          Infectious Diseases, Fort Detrick, MD.                                                 regulator-2 protein family. Biol. Cell 90: 239-245
                                                                                              2. Cordeiro-da-Silva A., Cardoso L., Tomas A., Rodrigues M., Cabral
    The sequence of the 63-kDa form of the Bacillus anthracis                                    M., Vergnes B., Sereno D., Ouaissi A. (2003). Identification of
protective antigen was codon-optimized for expression in the yeast                               antibodies to Leishmania silent information regulatory 2 (SIR2)
Saccharomyces cerevisiae. Large-scale fermentation of the antigen                                protein homologue during canine natural infections
produced intracellularly under these conditions yielded 300 µg
rPA63/mL culture medium with rPA63 comprising 12% of the total
yeast protein. The 63-kDa rPA purified under denaturing conditions
                                                                                                        DNA Vaccine Expressing D8L of Vaccinia Virus Enhanced the
demonstrated biological activity in a macrophage killing assay. Rabbits
and non-human primates (NHP) were immunized with the 63-kDa PA
and later challenged with a lethal dose of spores of the virulent Bacillus
                                                                                              P48       Efficacy of Milti-Gene Smallpox DNA Vaccine Formulations
                                                                                                        P. V. Sakhatskyy, S. Wang, T. Chou, S. Lu
anthracis Ames strain. Nineteen of twenty-nine rabbits receiving                                        University of Massachusetts Medical School, Worcester, MA.
recombinant yeast rPA63 survived, as did all five animals in a control
group immunized with the currently licensed anthrax vaccine. Five of                              Background: Most of the world’s population is naïve to poxvirus
six NHP that received the experimental vaccine, and two of three NHP                          infections. Live attenuated smallpox vaccines are under further
that received the control vaccine survived. All negative control animals                      investigation. The subunit vaccines (DNA or protein) is effective in
in both studies died. These results suggest that the 63-kDa form of PA                        animal studies but their immunogenicity needs further improvement
expressed in yeast is a promising candidate for a safe anthrax vaccine                        for human applications (1, 2). Identifying more potent protective
amenable to large-scale production.                                                           antigens will strengthen such approach. In this study, vaccinia protein
                                                                                              D8L has been tested for its immunogenicity and protection efficacy in
Reference:                                                                                    small animals. Methods: The D8L gene insert was produced from
1. Cook, J.C., et. al. Protein Expression and Purification 1998,                              VACV (WR strain) genome and subcloned into the DNA vaccine
   13:291-300                                                                                 vector pSW3891. New Zealand White rabbits or BALB/c mice received
                                                                                              four bi-weekly DNA immunizations with a gene gun. Immunized mice
                                                                                              were challenged ip with lethal dosage of VACV. Results: D8L DNA
                                                                                              vaccines were highly immunogenic and elicited strong anti-D8L IgG
                                                                                              responses in immunized rabbits and mice shown by ELISA, Western
P47       A Recombinant Leishmania Antigen Related to the Silent
          Information Regulatory 2 (SIR2) Protein Family Induces a B cell
          Activation and Antibody Specific Immune Response
                                                                                              Blot and IMV neutralization assays. D8L vaccine protected mice
                                                                                              against VACV challenge, either alone or in different multi-gene
          R. Silvestre1, A. Cordeiro-da-Silva1, A. Ouaissi2                                   smallpox DNA vaccine formulations. Superior efficacy of a formulation
          1
            Faculdade Farmácia and I.B.M.C. of Universidade Porto, Porto, PORTUGAL,           containing the D8L was demonstrated. Vaccinia immunoglobulin and
          2
            Institut de Recherche pour le Développement, UR008, Montpellier, FRANCE.          sera from mice that survived VACV challenge contained anti-D8L
                                                                                              antibody, supporting its role in vaccine induced immune protection.
    In previous studies, we have reported the characterization of a                           D8L DNA vaccine could induce antigen specific T cell responses with
Leishmania major gene encoding a protein (LmSIR2) with an extensive                           positive IFN-gamma by ELISPOT. Conclusions: D8L is a strong
homology to yeast SIR2p. This protein, a parasite excreted-secreted                           immunogen capable of eliciting protective antibody and cell mediated
antigen is expressed by different Leishmania species. Moreover, the                           immunity in small animals. It may serve as an excellent candidate to
immunogenicity of LmSIR2 was supported by the high reactivity of                              improve the existing subunit based smallpox vaccines.
sera from Leishmaniasis patients and dogs against LmSIR2
recombinant protein (rLmSIR2). In the present study, we have analysed                         References:
the effect of LmSIR2 on T and B murine cell populations. The results                          1. Hooper JW, Thompson E, Wilhelmsen C, et al. Smallpox DNA
presented showed that LmSIR2 targeted preferentially the B cells.                                vaccine protects nonhuman primates against lethal monkeypox. J
Indeed, in vitro assays showed that LmSIR2 activates B-cells as                                  Virol 2004;78(9):4433-43.
evidenced by increased expression of CD69 surface marker.                                     2. Fogg C, Lustig S, Whitbeck JC, Eisenberg RJ, Cohen GH, Moss B.
Furthermore, we found that in vivo injection of rLmSIR2 into BALB/c                              Protective immunity to vaccinia virus induced by vaccination with
mice induces a significant enhancement in the total number of spleen                             multiple recombinant outer membrane proteins of intracellular and
cells mostly due to the increase in the B-cell population when                                   extracellular virions. J Virol 2004;78(19):10230-7.
compared to the control mice, whereas the number of T cells remained
comparable to the control. Consequently, an antibody response could
be detected upon in vivo injection of rLmSIR2 with high levels of IgG,
mainly of IgG1 and IgG2a subclasses, when compared to IgM.                                                                                                   (continued)


                                                                                                                                                                     83
         Eighth Annual Conference
                              ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
          An Intranasal, Protollin™-RSV Subunit Vaccine Induces Mucosal                     immunizing mice, either alone or in combination. The immunogenicity
P49       IgA, Serum Neutralizing Antibodies and a Type-1 Cytokine-biased
          Response by Spleen and Lung Mononuclear Cells in Mice.
                                                                                            (ELISA), antibody specificity (immunoblot) and the bactericidal and
                                                                                            opsonophagocytic activities of the antibodies generated by these vaccines
          S. L. Cyr1, T. Jones2, I. Stoica-Popescu2, S. Chabot1, D. S. Burt2, B. J. Ward1   were investigated.
          1
            Microbiology and Immunology, McGill University, Montreal, PQ, CANADA,               The serogroup A OMV vaccine induced high levels of anti-OMV
          2
            ID Biomedical, Laval, PQ, CANADA.                                               IgG in mice, high bactericidal titres towards serogroup A strains of both
                                                                                            ST-5 and ST-7 from different African countries, and high
    There is currently no vaccine for respiratory syncytial virus (RSV), a                  opsonophagocytic activity. Serogroup W135 OMVs were also highly
major respiratory pathogen in children. A formalin-inactivated RSV                          immunogenic, and sera showed high bactericidal titres towards both
vaccine (FI-RSV) exacerbated disease in children who later became RSV                       serogroup W135 and C strains belonging to ST-11.
infected. This aberrant response was characterized by eosinophilia and a                        We therefore suggest that immunization with a serogroup A+W135
type-2 immune phenotype. Intranasal administration (IN) of                                  OMV mixture vaccine, either alone or combined with polysaccharide
Protollin™, a Proteosome™-based adjuvant, was shown to favor type-1                         antigens can protect against meningococcal disease caused by most
immunity in mice and to be safe in humans. Antigen enriched in RSV F                        serogroup A, C or W135 strains in Africa and may be an affordable T-
(fusion) and G (attachment) proteins was prepared from RSV-infected                         cell dependent alternative to conjugate vaccines.
Vero cultures by chromatography, formulated with Protollin and used to
immunize Balb/c mice (IN, 3 doses). Serum, bronchoalveolar lavage                           References:
(BAL), lungs and spleens were collected at euthanasia. Mean RSV-                            1. Norheim G, Høiby EA, Caugant DA, et al. Immunogenicity and
specific serum IgG titers measured by ELISA were significantly higher in                       bactericidal activity in mice of an outer membrane protein vesicle
mice immunized with the Protollin-formulated antigen compared with                             vaccine against Neisseria meningitidis serogroup A disease. Vaccine
those given antigen alone (P ≤ 0.001). Immunization with Protollin-                            2004; 22: 2171-80.
formulated antigen also elicited serum neutralization titers in excess of                   2. Tappero JW, Lagos R, Ballesteros AM, et al. Immunogenicity of 2
log2 7.75 as well as significant levels of RSV-specific IgA in BAL (P ≤                        serogroup B outer-membrane protein meningococcal vaccines: a
0.001 compared with mice given antigen alone). Spleen and lung                                 randomized controlled trial in Chile. JAMA 1999;281:1520-7.
mononuclear cells from mice immunized with Protollin-formulated
antigen spontaneously released up to 45 times more IFN_ into culture
supernatants than groups immunized with antigen alone, concomitant
with greatly reduced IL-5 production. These results suggest that an
intranasally delivered Protollin-formulated RSV vaccine may induce
protective immunity without the potentially adverse type-2 cytokine-
                                                                                            P51       Development and Use of the Outer Membrane Vesicle Concept for
                                                                                                      Vaccines Against Meningococcal Group B Disease
                                                                                                      E. Rosenqvist1, G. Norheim1, L. Meyer Næss1, P. Kristiansen1, P. Costantino2,
biased responses.                                                                                     E. Wedege1, D. A. Caugant1, B. Feiring1, I. S. Aaberge1, R. Rappuoli3, J. Holst1
                                                                                                      1
                                                                                                        Division for Infectious Disease Control, Norwegian Insitute of Public Health,
References:                                                                                           Oslo, NORWAY, 2Chiron Vaccines S.r.l., Siena, ITALY, 3Chiron Vaccine S.r.l., Siena,
1. Jones T, Cyr S, Allard F, Bellerose N, Lowell GH, Burt DS.                                         ITALY.
   Protollin™: a novel adjuvant for intranasal vaccines. Vaccine 2004;
   22:3691-3697.                                                                                Protein-based, outer membrane vesicle (OMV) vaccines have proven
2. Fries LF, Montemarano AD, Mallett CP, Taylor DN, Hale TL, Lowell                         to be efficacious against serogroup B meningococcal disease in Norway
   GH. Safety and Immunogenicity of a Proteosome-Shigella flexneri 2a                       and Cuba. Whereas such vaccines induce high levels of bactericidal
   lipopolysaccharide vaccine administered intranasally to healthy                          antibodies against homologous strains in all age groups, they are mainly
   adults. Infect. Immun. 2001;69:4545-4553.                                                strain-specific in infants. Currently, a public health intervention is
                                                                                            ongoing in order to control a serogroup B epidemic in New Zealand,
                                                                                            based on a B:4:P1.7b,4 production strain (MeNZB®). The upscaling
                                                                                            and standardization of the required vaccine production for controlling

P50       Prevention of Serogroup A, C and W135 Meningococcal Disease
          in the Meningitis Belt of Africa by Targeting Outer Membrane
                                                                                            the New Zealand epidemic has allowed the establishment of large-scale
                                                                                            GMP manufacturing for OMV vaccines . The outcome of this will be
                                                                                            the licensing of the vaccine in New Zealand and possibly in other
          Proteins
          E. Rosenqvist, G. Norheim, E. Fritzsønn, T. Tangen, P. Kristiansen,               countries.
          D. A. Caugant, A. Aase, E. A. Høiby, I. S. Aaberge                                    Pre-clinical and clinical data have been evaluated and compared for
          Division for Infectious Disease Control, Norwegian Institute of Public Health,    MenBvac® and MeNZB®, originally designed to control outbreaks in
          Oslo, NORWAY.                                                                     Norway and New Zealand, respectively. Data from these two
                                                                                            formulations and other experimental wild-type OMV preparations
    Epidemic meningococcal disease is recurrent in the Meningitis Belt                      provide an important basis for establishing international guidelines and
and is mainly caused by very homogenous clones of serogroup A                               regulatory consensus for such vaccines in the time to come. The
subgroup III (A:4/21:P1.20,9) or serogroup W135 and C (sequence                             availability of licensed OMV vaccines raises the question of whether this
type ST-11; 2a:P1.5,2). Although current vaccine approaches for these                       type of vaccines may provide the opportunity to control localized
serogroups target capsular antigens, non-capsular antigens such as outer                    outbreaks of serogroup B meningococci in other areas.
membrane proteins and lipopolysaccharides are also potential vaccine                        References:
candidates.
    Outer membrane vesicle (OMV) vaccines were developed from                               1. Tappero JW, Lagos R, Ballesteros AM, et al. Immunogenicity of 2
serogroup A and W135 strains with the same technique as for the                                serogroup B outer-membrane protein meningococcal vaccines: a
Norwegian serogroup B OMV vaccine (MenBvac®) and used for                                      randomized controlled trial in Chile. JAMA 1999;281:1520-7.


 84
   on Vaccine Research
                          ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
2. Holst J, Feiring B, Meyer Næss L et al. The concept of “tailor-made”,      reaction with mercaptoglycerol, followed by mild oxidation of the diol.
   protein based outer membrane vesicle vaccines against meningococcal        These aldehyde-modified proteins reacted with AO-derivatized
   disease. Vaccine 2005, in press.                                           polysaccharides to form conjugates via oxime linkages. Sera from mice
                                                                              immunized with a pneumococcal type 14 conjugate vaccine made using
                                                                              oxime chemistry had high anti-polysaccharide immune responses. The
                                                                              primary response could be boosted, indicating that the polysaccharide

P52       Reducing the Cost of Manufacturing Conjugate Vaccines;
          Effective Alternatives to Gel Filtration
                                                                              conjugate had characteristics of a T cell dependent antigen.

          A. Lees1, D. E. Shafer2
          1
            Biosynexus Inc, Gaithersburg, MD, 2None, Gaithersburg, MD.

     Vaccines consisting of capsular polysaccharides covalently linked to
proteins have been extremely effective at inducing humoral immunity.
                                                                              P54       Development of HIV-1 Subtype C Vaccine Candidates
                                                                                        P. Seth1, A. Arora1, P. Chugh1, S. Kumar1, P. Aggarwal1, V. Prasad1,
                                                                                        M. Vajpayee1, David Montefiori2
However, this class of vaccines is among the most expensive of the
                                                                                        1
                                                                                          Microbiology, All India Institute of Medical Sciences, New Delhi, INDIA,
childhood immunizations. Gel filtration is typically used to purify the
                                                                                        2
                                                                                          Department of Surgery, Duke University Medical Center, Durham, NC, USA.
high MW conjugate from free protein and lower MW polysaccharide, a
step which is slow and expensive, and which reduces yield. The use of             Since in India HIV-1 subtype C accounts for more than 95% of
mild, efficient linking chemistries (Lees et al., Vaccine 14:190, 1998)       HIV-1 infections, it is imperative that a vaccine based on the local
which minimize polysaccharide hydrolysis, and the fact that the same          circulating subtype should be designed. We cloned two envelope
protein used as the carrier is often added back as part of the final multi-   (gp120) gene and one gag protease gene of Indian HIV-1 subtype C
vaccine formulation, allowed us to evaluate alternatives to the gel           virus in the mammalian expression plasmid DNA vector ,pNK14, and
filtration step. In one approach, conjugate vaccines were cleaned-up          MVA (Modified Vaccinia Ankara) and evaluated these for
using dialysis only. Since the total amount of free protein may               immunogenicity in mice and in bonnet monkeys in ‘prime-boost
nevertheless be significant in multivalent vaccines such as S.                strategy format’. in which priming was done with rDNA vaccine
pneumoniae, it may be necessary to reduce the levels of unconjugated          constructs and boosting was done with rMVA constructs four weeks
protein. To address this, we developed a solid-phase method that rapidly      after priming. Immunized animals developed strong clade specific and
absorbs free protein but not the high MW conjugate (Shafer et al.             cross clade reactive humoral as well as cell mediated immune responses.
Vaccine 19:1547, 2001). Conjugate vaccines of S. pnuemoniae type 14           Humoral immune response was evaluated by ELISA and neutralizing
and N. meningiditis A and C capsular polysaccharides were processed by        antibody assay. The prime-boost regimen induced cross reacting
the usual gel filtration techniques, by simple dialysis or by the solid       neutralizing antibodies in monkeys against HIV-1 subtype C isolates
phase adsorption method. Yields of conjugate vaccine, based on                from early sero-converts from South Africa. Cellular immune response
polysaccharide recovery, were >90% for the latter two approaches but          was assayed by Cytotoxicity assay, ELISPOT assay and
typically <75% after gel filtration. Comparable anti-polysaccharide           Lymphoproliferative assay. Interestingly, the memory of the immune
antibody titers were induced in mice, regardless of the process method.       response was detected even beyond 6 months in mice and beyond 73
                                                                              months in monkeys. Immunized monkeys showed a very strong HIV-1
                                                                              subtype C specific recall immune response when challenged with MVA
                                                                              constructs 73 weeks after vaccination with two doses of DNA vaccine.
          Aminooxy Reagents and Oxime Chemistry for the
P53       Preparation of Conjugate Vaccines
          A. Lees, A. LopezAcosta
                                                                              References:
                                                                              1. Chugh P and Seth P. Induction of broad based immune response
          Biosynexus Inc, Gaithersburg, MD.                                      against HIV-1 subtype c gag DNA vaccine in mice. Viral
                                                                                 Immunology, 17, 2004 423-435.
    Covalent linkage of proteins to polysaccharides significantly             2. Kumar S and Seth P. Immunogenicity of Recombinant Modified
enhances the antibody response to the carbohydrate. We present a                 Vaccinia Ankara Viruses (rMVA) Expressing HIV-1 Indian Subtype C
versatile and efficient conjugation chemistry based on aminooxy (AO)             gag-protease and env-gp120 genes in Mice. Viral Immunol. 17, 2004,
reagents and oxime chemistry. Proteins and polysaccharides                       574-579.
functionalized with AO groups and aldehydes, respectively, were
covalently linked via oxime formation. To increase versatility, homo and
heterobifunctional aminooxy reagents, e.g., bis(AOAc)ethylenediamine
and N(AOAc)cysteamine, were prepared. Bis(AOAc) (ethylenediamine)
was used to functionalize protein carboxyls with AO groups.                   P55       Enhancement of Cell-mediated Immunity in Mice by the Model
                                                                                        of a Whole HIV-1 gag in Live Mycobacterium bovis BCG
                                                                                        D. Promkhatkaew
Alternatively, proteins were derivatized using a two-step protocol. In this
approach, a limited number of amines were bromoacetylated and then                      Department Of Medical Sciences, Nonthaburi, THAILAND.
reacted with (AOAc)cysteamine via a thioether linkage. These AO-
derivatized-proteins were subsequently reacted with oxidized                     Background: A recombinant live vector vaccine approach was
polysaccharides. The reverse linkage model was also employed, in which        focused to elicit a vaccine candidate of recombinant Mycobacterium bovis
AO-derivatized polysaccharides were linked to aldehyde-derivatized            BCG harboring a whole HIV-1 CRF01_AE gag DNA to investigate
proteins. Glycoproteins, like ovalbumin, could be oxidized under mild         specific cell-mediated immunities in BALB/c mice. Methods: The whole
conditions. Aldehydes were created on nonglycosylated proteins by             HIV-1 CRF01_AE gag sequence of 1,497 basepairs from Thai isolate
carbodiimide-mediated reaction with glyceric acid, followed by mild           was inserted into BCG. This live BCG was injected subcutaneously into
oxidation. Alternatively, amines were modified by bromoacetylation and                                                                                (continued)


                                                                                                                                                                85
         Eighth Annual Conference
                             ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
BALB/c mice once, and the spleen cells were investigated gag-specific                     infected humans.
cytotoxic T-lymphocyte (CTL) activity by Cr-55 release assay and
lymphocyte proliferation. Results: Construction of the stable expression                  References:
recombinant BCG was achieved that a cytoplasmic target protein of                         1. Stubbs AC, Martin KS, Coeshott C, Skaates SV, Kuritzkes DR,
approximately 55 Kd was detected by Western-blot. By single injection                        Bellgrau D, Franzusoff A, Duke RC, Wilson CC. Whole recombinant
of 0.1 mg of the recombinant BCG into mice, various specific CTL                             yeast vaccine activates dendritic cells and elicits protective cell-
responses were exhibited either against a single gag epitope of amino                        mediated immunity. Nature Med. 2001; 5:625-629.
acids 294-304 after 2 weeks, or widely recognition of various peptide                     2. Lu Y, Bellgrau D, Dwyer-Nield LD, Malkinson AM, Duke RC,
regions along the entire gag protein of moderate CTL activities (10-35%                      Rodell TC, Franzusoff A. Mutation-selective tumor remission with
specific cell lysis) and relatively high (50-68%), after one month.                          Ras-targeted, whole yeast-based immunotherapy. Cancer Res. 2004;
However, after two months, despite the remaining of CTL responses,                           64:5084-5088.
the activities were obviously 3-3.7 folds lower. These may trigger us to
try for a boost immunization with other vaccine vehicles containing the
same immunogen content to revert the CTL response in further study.
On the other hand, lymphocyte proliferation was also detected as 9.3
folds higher than that of non-immunized mice. Conclusion: Our results
demonstrate that BCG may be used as a live vector to induce cellular
                                                                                          P57       Analytical Challenges for Novel Vaccine Formulations
                                                                                                    E. Hartwell, S. D. Sen, B. J. Roser
                                                                                                    Cambridge Biostability Ltd, Cambridge, UNITED KINGDOM.
immunity to HIV-1 gag as introducing the vaccination in mice.
                                                                                              Thermostable vaccines have been developed using mixed sugar glass
References:                                                                               microspheres suspended in fluorinated liquids. The microspheres are
1. Honda M, Matsuo K, Nakasone T, et al. Protective immune responses                      insoluble in, and density matched with the liquid, producing physical
   induced by secretion of a chimeric soluble protein from a                              and chemically stable formulations. Analysis of polysaccharide vaccines
   recombinant Mycobacterium bovis BCG vector candidate vaccine for                       such as conjugate Haemophilus influenzae type b vaccine in such
   HIV-1 in small animals. Proc Natl Acad Sci USA 1995;92:1069                            formulations poses analytical challenges. The high sugar content is in
2. Ishii K, Ueda Y, Matsuo K, et al. Structural analysis of vaccinia virus                excess of the minute saccharide content under analysis. One method,
   DIs strain: Application as a new replication-deficient viral vector.                   used by the vaccine manufacturer, involved acid hydrolysis of
   Virol 2002;302:433-44.                                                                 polysaccharide to generate Ribitol and Ribose and the use of High
                                                                                          Performance Anion Exchange Chromatography with Pulsed
                                                                                          Amperometric Detection (HPAEC-PAD) to detect the non ionic sugar,
                                                                                          Ribitol. This appeared as a minute shoulder of the large peak of the

P56       Preclinical Development of Yeast-Based Immunotherapy for                        stabilising sugars. We have now developed a sample preparation and
          Chronic Hepatitis C Virus Infection                                             chromatographic method which has eliminated the interference of the
          A. A. Haller, T. King, Y. Lu, C. Kemmler, D. Bellgrau, G. Gordon, D. Apelian,   stabilising sugars so that the monomeric saccharide unit can be
          A. Franzusoff, T. C. Rodell, R. C. Duke                                         quantified.
          GlobeImmune Inc., Aurora, CO.                                                       Commercially available Haemophilus influenzae type b conjugate
                                                                                          vaccine with aluminium phosphate, was used. The vaccine was
    Background: Evidence suggests that control of hepatitis C infection                   formulated and spray dried to form 3 component mixed glass
in humans requires effective T cell-mediated immunity. Previous studies                   microspheres. These were suspended in an inert fluorinated liquid. The
have demonstrated that recombinant, heat-inactivated Saccharomyces                        chemical stability of the vaccine is determined as a measure of the
cerevisiae yeast (TarmogensTM) are avidly phagocytosed by and directly                    amount of free saccharide. It is expressed as percentage of the total
activate dendritic cells which present yeast-associated proteins to CD4                   saccharide content. The method we have developed uses a different
and CD8 T cells that are capable of mediating antigen-specific                            sample preparation which results in an ionic form of free saccharide, 5-
protective and therapeutic anti-tumor immunity. In this study,                            D-Ribitol-(1-1)-beta-D-Ribose-3-phosphate. An HPAEC-PAD method
Tarmogens that produce an HCV NS3-Core fusion protein (GI-5005)                           completely separates the ionic form from neutral stabilising sugars. This
were evaluated for their ability to induce protective and therapeutic                     method makes it possible to monitor stability of our novel formulations
immunity in mice. Methods: C57BL/6 and BALB/c mice were injected                          stressed up to 70ºC.
subcutaneously with GI-5005 and immunogenicity was determined
using assays that measure antigen-specific lymphocyte proliferation,
cytokine secretion, and cytotoxicity. A surrogate mouse model of HCV
infection employing HCV antigen-expressing syngeneic tumor cells was
used to assess preventative and therapeutic efficacy.
Results: Immunization with GI-5005 induced dose-dependent NS3 and
                                                                                          P58       Production and Control of a Brazilian Meningococcal C Conjugate
                                                                                                    Vaccine
                                                                                                    Silveira IAFB1, Bastos RC1, Neto MS1, Larangeira AP1, Fernandes SAR1,
Core antigen-specific helper and cytotoxic T cell activities that were                              Leal ML1, Silva WC1, Lee C-H2, Frasch C2 & Jessouroun E1
associated with secretion of IL-2, IFN-g, GM-CSF and TNF-a. Mice                                    1
                                                                                                      Laboratório de Tecnologia Bacteriana, Bio-Manguinhos, FIOCRUZ, RJ, Brazil
that were immunized either prior to or seven days after challenge with                              2
                                                                                                      Center for Biologics Evaluation and Research, FDA, Bethesda, USA
NS3-expressing tumor cells were protected against tumor formation.
No significant adverse effects have been observed upon repeated                              Meningococcal vaccines based on capsular polysaccharides induce
administration of Tarmogens in mice, rats, rabbit and macaques.                           short term protection in children and have been replaced by saccharide-
Conclusion: The GI-5005 Tarmogen was found to elicit protective                           protein conjugates. In Brazil, a conjugate vaccine has been developed
HCV-specific helper and cytotoxic T cell responses in mice. A Phase 1                     against the serogroup C by reductive amination (Jennings HJ &
study is being initiated to evaluate GI-5005 in chronically HCV-                          Lugowski C, Immunochemistry of groups A, B, and C meningococcal


 86
   on Vaccine Research
                             ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
polysaccharide-tetanus toxoid conjugates. J Immunol 1981; 127:1011-                                      Needle-Free Delivery of Antigens to Ultrasound Pre-treated Skin
1018). Different vaccine lots were obtained with the C polysaccharide
and tetanus toxoid. The aldehyde groups present in the activated-
                                                                                               P60       Demonstrated in a Feasibility Clinical Trial
                                                                                                         D. H. Libraty1, S. P. Barman2
polysaccharides by sodium periodate were measured by the purpald                                         1
                                                                                                           Center for Infectious Diseases & Vaccine Research, University of
method. The conjugation step was followed by SEC and 1HNMR                                               Massachusetts Medical School, Worcester, MA, 2Transdermal Drug Delivery ,
spectroscopy. The volumes were increased from 8 to 2,000 mL of final                                     Vaccines, Sontra Medical, Franklin, MA.
product in scale-up assays showing reproducibility of the production
procedures. One lot corresponding to 27,000 human doses                                            Introduction. Current immunizations involve needle-
(10_g/0.5mL) was used to prepare vials containing 5 lyophilized                                admininistered vaccines by IM/SC/ID routes. Skin immunization can
human doses in sterile conditions. All quality control assays required                         elicit robust immunity, due to the network of Langerhans cells in the
were satisfactory (WHO 2001. Recommendations for the production                                epidermis.
& control of meningococcal group C conjugate vaccines). In dose-                               We present a method to permeate the skin using an ultrasound device
response mice studies 1_g dose showed similar bactericidal activity                            (SonoPrep®), pre-topical delivery of vaccines. SonoPrep applies
and IgG titers to 10_g, but higher than the control group (plain                               ultrasound to a liquid that creates channels through the stratum
polysaccharide; ANOVA, p < 0.05). These results support production                             corneum. We report data from a clinical trial that determined delayed-
of clinical lots to be tested in phase I clinical studies this year.                           type hypersensitivity to antigens placed on skin permeated with
                                                                                               SonoPrep. Methods. The study was approved by the UMASS IRB. 20
References:                                                                                    volunteers, in two groups were enrolled in the study: (a) standard doses
1. Jennings HJ & Lugowski C, Immunochemistry of groups A, B, and                               of tetanus toxoid and Candida albicans antigens (ID), (b) identical doses
   C meningococcal polysaccharide-tetanus toxoid conjugates. J                                 of the same recall antigens over ultrasound-permeated sites. The antigen
   Immunol 1981; 127:1011-1018                                                                 was injected intradermally, into two sites (10 subjects). Results. The
2. WHO 2001. Recommendations for the production & control of                                   device was activated with a microprocessor performing conductivity
   meningococcal group C conjugate vaccines                                                    analysis to determine permeability, triggering device-turn off.<br /The
                                                                                               antigen was placed in the target reservoir. Indurations were measured at
                                                                                               48 h/96 h/7 days after application. Among twenty sites with SonoPrep,
                                                                                               one individual experienced discomfort at one site, other treated sites

P59       Production and Control of a Brazilian Meningococcal B Vaccine
          Jessouroun E1, Larangeira AP1, Pereira S1, Fernandes SA1, Nascimento DR1,
          Leal ML1, Gorla MC 2, Brandão A2, Simonsen V 2, Schenkmann RFP 3, Tanizaki
                                                                                               were sonicated with no adverse events. Tetanus toxoid and Candida
                                                                                               albicans recall antigens delivered by Sonoprep produced DTH responses
                                                                                               in 9/10 and 10/10 subjects. The kinetics of DTH responses were similar
          MM3, Frasch CE 4, Silveira IAFB1                                                     between the intradermal/Sonoprep groups. Conclusions. In conlusion,
          1
            Bio-Manguinhos, FIOCRUZ, Rio de Janeiro, RJ, Brazil                                immune responses were elicited to antigens delivered to SonoPrep-
          2
            Instituto Adolfo Lutz, SP, Brazil; 3 Instituto Butantan, SP, Brazil; 4Center for   treated skin.
          Biologics Evaluation and Research, FDA, Bethesda, USA.
                                                                                               References:
In Brazil serogroup B accounts for 60% of total clinical isolates from                         1. Glenn GM et.al. Transcutaneous immunization and
meningococcal infections (Jessouroun E et al., Vaccine 2004; 22:2617-                             immunostimulant strategies: capitalizing of the immunocompetence
2625). Brazilian research institutions have collaborated to develop a                             of the skin. Expert Rev Vaccines 2:253-67, 2003
group B meningococcal vaccine composed of detergent treated-OMV                                2. Samir Mitragotri, Joseph Kost, 2004. “Low Frequency Sonophoresis:
and dLOS. The antigens were purified from bacterial biomass harvested                             A Review”, Advanced Drug Delivery Reviews, 56, 589-601
from 100L bioreactor batches. In antigen presentation stability studies,
lyophilized vaccine seems to be more stable than liquid.
Immunogenicity results from studies of the vaccine in mice were
promising, showing less reactogenicity and pirogenicity than a Cuban                                     Anaphylaxis Following Recombinant Hepatitis B Vaccines in
meningococcal B vaccine (Vamengoc®). The inflammatory potential of
both vaccines was studied in rabbits and showed leucocytosis after each
                                                                                               P61       Yeast-Sensitive Individuals: Reports to VAERS
                                                                                                         L. DiMiceli1, V. Pool1, S. V. Shadomy2, J. Iskander1
intramuscular injections (three doses). The increase of total leukocyte                                  1
                                                                                                           CDC/National Immunization Program, Atlanta, GA, 2CDC/National Center for
count, induced by Brazilian vaccine was short lasting with reduction of                                  Infectious Diseases, Atlanta, GA.
measured levels lasting up to 7 days while Cuban vaccine tended to
maintain somewhat elevated leukocyte levels 7 and 30 days after                                    Background: Theoretical concerns exist over recombinant Hepatitis
immunization. The quality control methodologies were also revised and                          B vaccination (HBV) of yeast-sensitive individuals (YSI). Per the
the product presented satisfactory results compared to similar vaccines                        Advisory Committee on Immunization Practices, the presence of
(Fredrikssen JH et al., NIPH Annals 1991; 14:67-78). These results                             allergies to baker’s yeast is listed as a contraindication for HBV. We
support production of clinical lots to be tested in phase I studies this                       evaluated reports to the Vaccine Adverse Event Reporting System
year.                                                                                          (VAERS) for anaphylaxis following HBV in YSI. Methods: We searched
                                                                                               the entire VAERS database for reports received from July 1990 to July 1,
                                                                                               2004 mentioning a history of allergies to yeast. We classified cases which
                                                                                               described a history of yeast allergies as probable or possible anaphylaxis
                                                                                               based on previously published criteria. Probable anaphylaxis was defined
                                                                                               as >1 dermatologic symptom(s) and >1 respiratory, gastrointestinal, or
                                                                                               cardiovascular symptom(s) with onset <4 hours of vaccination. Possible
                                                                                                                                                                       (continued)


                                                                                                                                                                                87
         Eighth Annual Conference
                           ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
anaphylaxis was defined as >1 dermatologic or respiratory symptom(s)                          CAP Absorbed rPA Nasal Vaccine as an Approach to Mucosal
with onset <4 hours of vaccination, or as >1 dermatologic and
respiratory symptoms within 4-12 hours of vaccination. Results: We
                                                                                    P63       Immune Protection Against Anthrax Infection
                                                                                              P. Nagappan1, J. Arroyo2, T. Morcol1, A. R. Mitchell1, L. Nerenbaum1,
identified 107 reports which mentioned yeast allergies. Out of 11                             S. Billingsley1, S. J. D. Bell1
potential anaphylaxis cases identified after HBV or in combination with                       1
                                                                                                BioSante Pharmaceuticals, Inc., Smyrna, GA, 2DVC LLC a CSC Company,
HBV, four met the probable case definition. The age range was 10-50                           Frederick, MD.
years, three were classified as serious per FDA regulations, and the
majority was female. No deaths were reported. Conclusions: Although                      The spore-forming bacterium Bacillus anthracis is considered to be a
the number of vaccinated YSI is unknown, the number of definite                     likely biological warfare agent1. Anthrax spores can easily be transmitted
reported life-threatening anaphylactic reactions in YSI following HBV is            via the air, as evidenced by the post 9/11 terrorist attacks in the USA.
few. Further studies investigating the possible role of yeast in the                The current anthrax vaccine licensed for use in the United States is
pathophysiology of vaccine-associated anaphylaxis should be                         Anthrax Vaccine Absorbed, an aluminum hydroxide-adjuvanated
undertaken.                                                                         vaccine administered subcutaneously2. Our goal is to avoid the use of
                                                                                    aluminum adjuvant and to develop alternatives to injectable vaccines.
References:                                                                         The BioSante proprietary calcium phosphate (CAP) nanoparticle system
1. Greenburg DP. Pediatric Experience with Recombinant Hepatitis B                  is a proven non-injectable adjuvant. In the present study, recombinant
   Vaccines and Relevant Safety and Immunogenecity Studies. Pediatr                 Protective Antigen (rPA) adjuvanated with CAP was delivered across the
   Infect Dis J 1993; 12:438-45.                                                    mucosal surfaces of the upper airways. As a reference standard, the rPA
2. Wiedermann G, Scheiner O, Ambrosch F, et al. Lack of Induction of                was combined with Alhydrogel (aluminum hydroxide gel). Both CAP
   IgE and IgG Antibodies to Yeast in Humans Immunized with                         and Alhydrogel formulations were administered intranasally (IN) to
   Recombinant Hepatitis B Vaccines. Int Archs Allergy Appl Immun                   Balb/c mice using one primary and two booster IN vaccinations.
   1988; 85:130-132.                                                                Immunogenicity was monitered over 14 weeks. No mortality or
                                                                                    morbidity was noted during this study. Serum was collected from bi-
                                                                                    weekly blood samples and analyzed by ELISA. After nasal delivery, the
                                                                                    anti-rPA IgG ELISA results indicated that the CAP-based vaccine
          Histopathology Analysis of Local Reactions in Mice following
P62       Injection of Diphtheria-Tetanus-Acellular Pertussis (DTaP) vaccines
          A. Honjo, T. Katsuta, S. Tateyama, C. Nagaoka, T. Tokutake, Y. Arimoto,
                                                                                    induced a stronger, faster and longer-lasting immune response than
                                                                                    Alhydrogel-adjuvanated rPA or rPA alone. Therefore, our CAP-rPA
                                                                                    anthrax vaccine candidate appears to be a safe and potent inducer of
          N. Nakajima, T. Goshima, T. Kato                                          humoral immunity after IN delivery.
          St.Mariannna University School of Medicine, Kawasaki-si, JAPAN.
                                                                                    References:
    Background: In Japan, diphtheria tetanus acellular pertussis (DTaP)             1. Klemm DM, Klemm WR. A history of anthrax. J Am Vet Med Res
vaccines have been used . The rate of severe adverse events has been                   1959; 135: 458
reduced. However, redness and/or swelling reactions are still presented             2. Pittman PR, Kim-Ahn G, Pifat DY, et al. Anthrax vaccine:
and the mechanisms causing these reactions have not been elucidated.                   immunogenicity and safety of a dose-reduction, route-change
Therefore, we injected separately and observed histopathology changes                  comparison study in humans. Vaccine 2002; 20: 1412-20
at the injection site of: diphtheria tetanus acellular pertussis (DPT),
diphtheria tetanus toxoids (DT), tetanus toxoids (T), thimerosal,
aluminum chloride, and formalin.
Methods: Eight-week-old male ICR strain SPF mice were used. Mice
were injected subcutaneously with 0.5 ml of each vaccine or with an                 P64       Influenza Nucleoprotein Conjugated to Immunostimulatory
                                                                                              DNA as a Potential Vaccine Against Pandemic Influenza
                                                                                              T. dela Cruz1, D. Higgins1, G. Ott1, I. Mbawuike2, S. Tuck1, G. Van Nest1
additive at their shaved abdomen. Mice were injected twice at 4-week
intervals. One week after the second injection, all the mice were
                                                                                              1
                                                                                                Dynavax Technologies, Berkeley, CA, 2Baylor College of Medicine,
sacrificed and their tissues were surgically removed from the injection                       Houston, TX.
sites. Results: In macroscopic findings, we found major axis indurations
of approximately 5 mm in diameter in each of the DPT, DT, and T                         Background: A highly immunogenic, conserved influenza antigen
groups. There were no macroscopic changes in the three groups                       could serve as a first-line vaccine defense against divergent or pandemic
receiving additives. In histopathology examinations, we detected the                strains. Immunization of mice with influenza nucleoprotein (NP)
cellular infiltration of neutrophils suggesting an inflammation, and                provides protection against divergent influenza stains. Linkage of
eosinophils or histiocytes suggesting an allergy. The DPT group                     immunostimulatory DNA (ISS) to antigens significantly enhances
presented the most cellular infiltration. Conclusions: These results                antigen-specific cellular and humoral responses. NP linked to ISS (NP-
suggest that local reactions depend on various factors rather than a                ISS) is expected to induce strong Th1 and CTL responses that can
single one, and have relevance to inflammation and allergy.                         provide cross-protection against widely divergent A strains. NP-ISS may
                                                                                    also enhance responses to other co-delivered viral antigens such as
Reference:                                                                          hemagglutinin (HA). Methods: Mice were immunized twice with NP-
1. Norihisa Goto and Kiyoto Akama. Histopathological Studies of                     ISS ± split monovalent flu vaccine and bled two weeks after each
   Reactions in Mice Injected with Aluminum-Adsorbed Tetanus                        immunization for anti-NP and anti-HA isotype analysis. Spleens were
   Toxoid. Microbiol.Immunol. 1982; 26: 1121-1132._______                           harvested to evaluate NP-specific and HA-specific cell-mediated
                                                                                    immune responses via ELISA, ELISPOT, and CTL. Statistical
                                                                                    significance calculated using one-way ANOVA with the Kruskal-Wallis
                                                                                    and Dunn’s Multiple Comparison tests. Results: Immunization with
                                                                                    NP-ISS induced high antigen-specific IgG2a (p<0.01) and IFN_

 88
   on Vaccine Research
                            ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
responses (p<0.01), while immunization with NP alone induced                                         A Novel Subunit Vaccine Protects Mice Against Yersinia Infection
predominantly IgG1 and IL-5. IFN_ ELISPOT data showed significant
NP-specific CD8+ IFN_ response (p<0.001), and Cr-51 release assays
                                                                                          P66        L. Wonderling1, D. Straub2, D. Emery2
                                                                                                     1
                                                                                                       Syntiron, Saint Paul, MN, 2Epitopix, Willmar, MN.
showed significant cytotoxic activity was induced in the conjugate
immunized mice (p<0.001). Co-delivery of NP-ISS and split vaccine                             The genus Yersinia consists of three human pathogens; Y. pestis is the
significantly enhanced overall HA antibody titers (p<0.01).                               causative agent of plaque, while Y. pseudotuberculosis and Y. enterocolitica
Conclusions: Immunization with NP-ISS induces potent Th1 and CTL                          primarily cause gastrointestinal illnesses. Due to concerns that Y. pestis
responses, as well as enhancing response to HA when co-delivered with                     may be used as a potentially deadly bio-weapon, there has been
split vaccine. This vaccine shows great potential to induce protective                    considerable research aimed at identifying new antigens for a plague
immunity against divergent and potentially pandemic influenza strains.                    vaccine. Since the three Yersinia species utilize similar pathogenic
                                                                                          strategies during infection of mice, the more innocuous Y. enterocolitica
References:                                                                               species was used for initial investigations into Y. pestis vaccine
1. Mbawuike I, et al. A baculovirus–expressed influenza A/Udorn                           candidates. In the current study, membrane proteins were isolated from
   (H3N2) nucleoprotein induces protective T cell immunity against                        Y. enterocolitica grown under iron-limiting conditions and formulated
   influenza A/H3N2 and A/H1N1 in mice. Vaccine Research 1994;                            into a subunit vaccine. These proteins were selected as candidate
   3:211-227.                                                                             antigens due to their large size, surface exposure, and their documented
2. Tighe H, et al. Conjugation of a protein to immunostimulatory DNA                      expression during infection. The vaccine was then tested in a mouse
   results in rapid, long-lasting and potent induction of cell-mediated                   model of systemic infection. Following intraperitoneal vaccination, mice
   and humoral immunity. Eur J Immunol 2000; 30(7):1939-47.                               were challenged in the lateral tail vein with Y. enterocolitica. None of the
                                                                                          control mice survived challenge; however, 100% of the vaccinated mice
                                                                                          survived with no observed morbidity (p<0.0001). These results
                                                                                          suggested that one or more of the proteins present in the vaccine were
P65       Development of SARS Vaccine Using Recombinant Vaccinia Virus
          Derived from LC16m8
          M. Kitabatake1, F. Yasui2, S. Inoue3, K. Morita3, F. Murai4, M. Kidokoro5,
                                                                                          highly protective against systemic challenge. Studies using matrix-
                                                                                          assisted laser desorption ionization time-of-flight mass spectrometry
          K. Mizuno6, H. Shida7, K. Matsushima1, M. Kohara2                               identified several proteins in this composition as outer membrane iron
          1
            Univ. Tokyo, Tokyo, JAPAN, 2The Tokyo Metro. Inst. Med. Sci., Tokyo, JAPAN,   acquisition proteins that are well-conserved among the pathogenic
          3
            Inst. Tropical Med., Nagasaki Univ., Nagasaki, JAPAN, 4Post Genome Inst.,     Yersinia. Taken together, the results of our investigations indicate that
          Tokyo, JAPAN, 5Natl. Inst. Infect. Dis., Tokyo, JAPAN, 6The Chemo-Sero-         protein components of the Y. enterocolitica membrane from bacteria
          Therapeutic Res. Inst., Kumamoto, JAPAN, 7Inst. Gen. Med., Hokkaido Univ.,      grown under iron-limiting conditions may be effective as antigens for
          Sapporo, JAPAN.                                                                 vaccination against plague.

    Background. Severe acute respiratory syndrome (SARS) caused by                        References:
novel type coronavirus (SARS-CoV) first emerged in China and spread                       1. Brubaker, R.R. 1991. Factor promoting acute and chronic diseases
to 29 countries, resulting in over 800 people death. Methods. We                             caused by Yersiniae. Clin. Microbiol. Rev. 4:309-324.
generated SARS-CoV spike protein expressing recombinant vaccinia                          2. Carniel, E. 2001. The Yersinia high-pathogenicity island: an iron-
virus (RVV) derived from its highly attenuated strain LC16m8. We                             uptake island. Microbes Infect. 3:561-569.
performed the in vitro neutralizing assay against SARS-CoV or vaccinia
virus (VV) using serum from rabbits intradermally immunized with RVV
or LC16m8. Also we confirmed the efficacy of RVV against the rabbits
which were pre-immunized with LC16m8. Results. RVV, but not
LC16m8, induced the neutralizing (NT) antibody against SARS-CoV in                        P67       Cysteine Proteinases Vased Vaccines for L. major and
                                                                                                    L. infantum Infections
                                                                                                    S. Rafati, T. Taheri, A. Zadeh Vakili, A. Nakhaee, F. Zahedifard, Y. Taslimi,
rabbits from one week after injection, and the NT titer increased about
100 times. At two weeks after boost injection, the NT titer increased by                            F. Doustdari
10 times further. In the rabbits pre-immunized with LC16m8, the NT                                  Immunology, Pasteur Institute of Iran, Tehran, IRAN.
antibody against SARS-CoV could be similarly induced by inoculation of
RVV in spite of the presence of the NT antibody against VV.                               Recently, we have evaluated the cysteine proteinases type I and II of
Conclusions. RVV highly induces the NT antibody against SARS-CoV                          L. infantum using a heterologous prime-boost regime for vaccination
by single injection. RVV provides the protective immunity against SARS-                   against experimental visceral leishmaniasis in dogs. Following
CoV by overcoming the immunity against VV. RVV derived from                               vaccination and challenge, dogs were followed for 12 months. All dogs
LC16m8 can be powerful vaccine against SARS even for the people who                       vaccinated by prime/boost with DNA/recombinant CPs (in
were previously inoculated with smallpox vaccine.                                         combination with CpG ODN and Montanide 720), remained free of
                                                                                          infection in their bone morrow. In contrast, three out of four dogs
References:                                                                               (75%) in the control groups had infection in their bone marrow. The
1. Jin NY, Funahashi S, Shida H. Constructions of vaccinia virus A-type                   peripheral lymphocytes from protected animals had generally higher
   inclusion body protein, tandemly repeated mutant 7.5 kDa protein,                      proliferation responses to F/T antigen, rCPA and rCPB than controls.
   and hemagglutinin gene promoters support high levels of expression.                    Analysis of cytokine mRNA level suggested that vaccinated dogs had
   Arch Virol. 1994;138:315-30.                                                           elevated IFN-_ mRNA in PBMC whereas there was a consistent increase
2. Ohishi K, Inui K, Barrett T, Yamanouchi K. Long-term protective                        in the level of IL-10 in the control groups and some vaccinated dogs.
   immunity to rinderpest in cattle following a single vaccination with a                 The ratio of IgG2/IgG1 against all three antigens (F/T, rCPA and rCPB)
   recombinant vaccinia virus expressing the virus haemagglutinin                         in vaccinated dogs was always higher than in control dogs. We also
   protein. J Gen Virol. 2000 81:1439-46.                                                                                                                             (continued)


                                                                                                                                                                                89
          Eighth Annual Conference
                              ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
                                                                                       P69
showed that with the exception of one dog, all dogs in the vaccinated                            Protection Studies with Candidate Schistosoma mansoni
group in compare to control dogs had strong DTH responses. We                                    DNAVaccines
propose that the combination of DNA and recombinant protein                                      A. M. Karim1, N. El-Ghazali1, A. Medhat1, S. F. Ibrahim2
vaccination using CPs could be instrumental to control VL in dogs.                               1
                                                                                                   Ain Shams Univ. Fac. of Science, Cairo, EGYPT, 2Cairo Univ. Fac. of Science,
                                                                                                 Cairo, EGYPT.

                                                                                           Schistosomiasis is a debilitating often deadly parasitic disease

P68       Development of Attenuated Mutants as Potential Vaccine
          Candidates for Visceral Leishmaniasis
          P. Salotra1, G. Sreenivas 2, R. Singh1, A. Selvapandiyan3, R. Duncan3,
                                                                                       afflicting hundreds of millions of people worldwide. The development of
                                                                                       a vaccine offers hope for effective long term control. In animal studies,
                                                                                       native and recombinant antigens have consistently failed to induce high
          H. L. Nakhasi3                                                               levels of protection as observed with irradiated live vaccine. In this study
          1
            Institute of Pathology (ICMR), New Delhi, INDIA, 2 Insitute of Pathology   antigens previously shown to be associated with the tegument of the
          (ICMR), New Delhi, INDIA, 3CBER, FDA, Bethesda, MD.                          schistosomule (1, 2) have been compared for their efficacy in inducing
                                                                                       protection by DNA vaccination. C57BL6 mice were immunized 3 times
    Background: Visceral Leishmaniasis (VL), a fatal disease caused by                 at 4 week intervals with 125 µg of pcDNA encoding phosphoglycerate
Leishmania donovani, is endemic in parts of India and Sudan.                           kinase (SmPGK), Sm20.8, Tropomyosin (SmTM1), SmCalponin, Sm23,
Understanding the mechanisms of Leishmania virulence and                               or a cocktail of the 5 antigens. Mice were challenged with 150 S. mansoni
development of vaccines is essential for eradication of the disease. We                cercariae 5 weeks after the last immunization and worms were collected
have employed microarray technology for a rapid discovery of virulence-                by liver perfusion 8 weeks later. Compared to a control group injected
related genes, with the goal of preparing gene knockouts of selected                   with saline, significant protection levels of 26-33%, 32-40%, 24-31%
genes. Such mutant parasites, with known gene defects, have great                      and 16-20% were observed for mice groups immunized with SmPGK,
potential to be used as live, attenuated vaccines. Methodology: Gene                   Sm20.8, Sm 23 and cocktail respectively. In a second study mice groups
expression was analysed in promastigote and amastigote stages of Indian                were immunized twice with 200 µg pcDNA encoding SmCyclophilin, a
isolates of L. donovani using genomic microarrays comprising ~ 5000                    fragment of SmFilamin or SmFilamin combined with recombinant
clones1. The data was analysed by Acuity software. Deletion mutants                    Filamin protein. Significant protection levels of 14%, 15% and 19%
were prepared by double homologous gene replacement using                              respectively were observed. Those results demonstrate the potential for
hygromycin and neomycin cassettes2. Results: Gene expression analysis                  induction of protective immune responses using DNA constructs
led to identification of over one hundred differentially expressed clones.             expressing schistosome tegumental antigens.
Sequence analysis of clones abundantly expressed in amastigotes revealed
homology to certain novel as well as known genes (NAD/FAD                              References:
dehydrogenase, reductase, gp46, gp63, amastin etc). One growth                         1. Lee KW, Shalaby KA, Thakur KA, et al. Cloning the gene for
regulated gene, Centrin was targeted for deletion in Leishmania                           phosphoglycerate kinase from Schistosoma mansoni and
parasite2. Centrin double knockout mutants showed selective growth                        characterization of its gene product. Mol Biochem Parasitol 1995; 71:
arrest as amastigotes but not as promastigotes. The null mutants failed                   221-231.
to survive in the amastigote stage in vitro as well as in vivo, indicating an          2. Kiang D, El-Ghazalie NE, Medhat, AM, et al. Identification and
important role for centrin in parasite growth. The centrin knock out                      characterization of Schistosoma mansoni p17.7 , a cyclophilin. Mol
mutant, generated with an Indian field isolate of VL, is under evaluation                 Biochem Parasitol 1996; 76: 73-82.
in animal model as a vaccine against VL. Conclusion: Several virulence-
related genes were identified as targets for gene disruption to develop an
attenuated vaccine against VL. Centrin gene knockout parasites that fail
to proliferate as amastigotes provide a promising candidate as a live,
attenuated vaccine against VL.
                                                                                       P70       Protective Immunity of Single and Multiple Recombinant DNA or
                                                                                                 Protein Vaccines Against Lymphatic Filariasis.
                                                                                                 P. Kaliraj, Sr.1, S. Anand1, V. Murugan1, K. KirthikaA2, M. Reddy2
                                                                                                 1
                                                                                                   Anna University, Chennai, INDIA, 2MGIMS, Sevagram, INDIA.
References:
1. Duncan R, Salotra P, Goyal N et al. The application of gene
                                                                                           Background: There is a need to develop suitable Immunoprophylactic
   expression microarray technology to kinetoplastid research Curr. Mol.
                                                                                       agent for elimination of lymphatic filariasis.In this study we report that
   Med.2004; 4:611-621.
                                                                                       the dual DNA antigen expression construct or cocktail Protein
2. Selvapandiyan A, Debrabant A, Duncan R, et al. Centrin gene
                                                                                       vaccination induces stronger immune responses and higher protection
   disruption impairs stage-specific basal body duplication and cell cycle
                                                                                       than those of an single antigen DNA/Protein (ALT or VAH) in jirds.
   progression in Leishmania. J. Biol. Chem.2004; 279:25703-25710.
                                                                                       Methods: B.malayi L3 expressed genes BmALT2 and BmVAH were
                                                                                       inserted individually in eukaryotic expression vector (pVAX) and
                                                                                       combinely in dual antigen expression eukaryotic vector(pBUDCE4).
                                                                                       Jirds immunized with single recombinant DNA/Protein or with
                                                                                       combination of two DNA/ proteins by IM/IP injection. In vivo parasite
                                                                                       clearance study with individual or combinational DNA/Proteins by
                                                                                       micropore chamber against B.malayi larvae. spleenocyte proliferation
                                                                                       level was checked by MTT assay.Cytokines response was evaluated by
                                                                                       RT-PCR. The statically significance of group difference was assessed by
                                                                                       student ‘t’ test. Results: Jirds produced higher antibody responses against
                                                                                       dual antigen constructs compared to single antigen construct. Similarly
                                                                                       in vivo micropore chamber cytotoxicity study using Jirds challenged with

 90
   on Vaccine Research
                            ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
multiple antigen (pBUD ALT-VAH) showed higher (p<0.01) protection                                 Canine Herpesvirus Bacterial Artificial Chromosome Technology For
(63-70%) than single vaccine construct i.e pVAX ALT or pVAX VAH
(50-60%). Similarly cocktail of two recombinant proteins rALT+rVAH
                                                                                        P72       Antifertility Vaccination of Foxes in Australia
                                                                                                  T. Strive, J. Wright, N. French, C. M. Hardy, G. H. Reubel
showed higher protection i.e., 80 % (p<0.01) than single protein vaccine                          Sustainable Ecosystems, CSIRO, Canberra ACT, AUSTRALIA.
rALT or rVAH (61-72%). Cytokine analysis of the immunized animals
showed that recombinant proteins induced Th2 type of response whereas                       European red foxes are a major pest in Australia that threaten the
DNA vaccination biased towards Th1 type response. Conclusion: Our                       survival of native wildlife and reduce lamb production through
results show that dual antigen DNA vaccination with pBUD ALT-VAH                        predation. The most commonly used method to control foxes is by
or vaccination with cocktail protein elicit higher protective immune                    poisoning with sodium mono-fluoroacetate (1080) baits, but this is
response against B.malayi infection in jirds than single antigen                        considered non-specific, expensive and unsuitable for certain situations
DNA/Protein vaccination. The protective efficacy of the recombinant                     (e.g. urban areas). Antifertility vaccination on the other hand is
protein was found to be better than that of DNA vaccine.                                recognized as a humane, non-lethal approach to reduce animal numbers
                                                                                        and thus their impact. The principle of this method is to induce
References:                                                                             autoimmune responses against proteins in the reproductive tract with
1. William.F.Gregory, Rick.M.Maizels, et al. The abundant larval                        the aim to interrupt fertilization.
   transcript 1&2 genes of brugia malayi encode stage specific candidate                    We have selected canine herpesvirus (CHV) as the preferred vector
   vaccine antigen for filariasis. Infection and immunity; July                         to deliver contraception for three reasons. Firstly, viral vectors have been
   2000,p4174-4179.                                                                     shown to be effective at delivering immunocontraception to pest
2. Janice Murray, Rick.M.Maizels, et al. Expression and immune                          animals. Secondly, CHV is specific to canids, so greatly increasing
   recognition of brugia malyi VAL-1, a homologue of vespid venom                       specificity, and finally, the population of Australian foxes is highly
   allergen& ancylostoma secreted proteins. Molecular and Biochemical                   susceptible to CHV infection. We have demonstrated that infectious
   parasitolgy, Nov2001;118(1):89-96                                                    recombinant CHVs can be readily produced using BAC technology.
                                                                                        Transgenes, including a green fluorescent marker protein gene and fox
                                                                                        and porcine oocyte zona pellucida genes were inserted into CHV in
                                                                                        either the thymidine kinase gene or an intergenic region between
                                                                                        glycoprotein H and UL21a. All rCHVs produced as BACs were
P71       Enhancing Brucellosis Vaccines, Vaccine Delivery Systems and
          Surveillance Diagnostics for Bison and Elk in the Greater
          Yellowstone Area
                                                                                        recovered as infectious recombinant viruses with similar cytopathic
                                                                                        effects as wild-type CHV following transfection of BAC DNA into
          G. E. Plumb, Jr.1, B. Marsh2                                                  canine cells. The expression of transgenes by rCHVs was confirmed in
          1
            Yellowstone National Park, US National Park Service, Yellowstone National   vitro by immunostaining of infected cell cultures and by Western blots.
          Park, WY, 2Board of Animal Health, State of Indiana, Indianapolis, IN.
                                                                                        References:
    The Greater Yellowstone Area (GYA) is one of the largest intact                     1. Reubel GH, Pekin J, Venables D, Wright J, Zabar S, Leslie K, et al.
ecosystems in the world. It consists of 28,000 square miles in the states                  Experimental infection of European red foxes (Vulpes vulpes) with
of Montana, Idaho, and Wyoming. The GYA is also home to the largest                        canine herpesvirus. Vet Microbiol 2001;83(3):217-33.
wild elk (125,000) and bison (5,000) populations in North America                       2. Reubel GH, Pekin J, Webb-Wagg K, Hardy CM. Nucleotide
which are chronically infected with brucellosis (Brucella abortus). These                  sequence of glycoprotein genes B, C, D, G, H and I, the thymidine
wildlife are recognized as the last large reservoir of B. abortus in the                   kinase and protein kinase genes and gene homologue UL24 of an
United States (elk 2-30% seroprevalence and bison 40-80% sero                              Australian isolate of canine herpesvirus. Virus Genes 2002;25(2):195
prevalence) and there is strong concern about disease transmission to
area livestock. To date, wildlife brucellosis vaccination and diagnostic
programs are derivative of techniques developed for livestock (Schurig
                                                                                                  Molecular Cloning and Sequence Analysis of Bm86 cDNA
2002). The brucellosis vaccine RB51 has been demonstrated to confer
moderate protection against spontaneous pathogenic abortion in bison                    P73       from a Thai Strain of the Cattle Tick, Boophilus microplus
                                                                                                  S. Jittapalapong1, S. Thanasilp1, T. Sirinarukmitr2, K. Kaewmongkol3,
(~70%), but little protection against fetal or maternal infection (~25%).
Thus, while vaccination in bison or elk must be one part of an overall                            R. W. Stich4
strategy to control or eliminate B. abortus in the GYA, much research is
                                                                                                  1
                                                                                                    Veterinary Parasitology, Kasetsart University, Bangkok, THAILAND,
needed before current vaccines can be judged adequate for use in these
                                                                                                  2
                                                                                                    Veterinary Pathology, Kasetsart University, Bangkok, THAILAND, 3Veterinary
species (NRC 1998). There are strategically important gaps regarding                              Companion Animal Medicine, Kasetsart University, Bangkok, THAILAND,
vaccines, vaccine delivery systems, and surveillance diagnostics
                                                                                                  4
                                                                                                    Veterinary Preventive Medicine, The Ohio State University, Columbus, OH.
developed for the specific immunology of wild and free-ranging bison
and elk. This abstract reports on a Special Committee of The United                         Boophilus microplus is the most important ectoparasite of livestock in
States Animal Health Association that is evaluating vital data and                      Thailand, and is responsible for severe economic losses due to direct
proposing overarching research strategies for enhancing wildlife                        effects of feeding and through transmission of pathogens. Extensive
brucellosis vaccines.                                                                   acaricide use to control these ticks has drawbacks such as selection for
                                                                                        pesticide resistance and contamination of the environment and animal
References:                                                                             products. A Bm86-based anti-tick vaccine has shown promise for tick
1. Cheville NF, McCullough DR, Paulson LR. Brucellosis in the Greater                   control in other countries. The purpose of this work was to characterize
   Yellowstone Area. National Academy Press 1998.                                       Bm 86 from a Thai strain of B. microplus to determine if this vaccine
2. Schurig GG, Sriranganathan N, Corbel MJ. Brucellosis vaccines: past,                 could be feasible in Thailand. Ticks were collected from dairy cattle in
   present, and future. Vet Microbiol 2002 90:479-496.                                                                                                           (continued)


                                                                                                                                                                           91
         Eighth Annual Conference
                          ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
Thailand, mRNA was isolated from B. microplus midgut samples, cDNA                      CpG Oligodeoxynucleotides Upregulate Antibacterial Systems
was amplified with Bm86-specific primers and amplicons were cloned
into the pFastBacHTB vector for sequencing and analysis with the
                                                                             P75        and Induce Early, Non-specific Antiviral Protection in Fish.
                                                                                        A. C. Carrington1, B. Collet2, C. J. Secombes1
Wisconsin Package. The 2,194 bp insert contained a 1,953 bp open                        1
                                                                                          Department of Zoology, University of Aberdeen, Aberdeen, UNITED
reading frame, and the Thai strain Bm86 protein sequence was 92.0 and                   KINGDOM, 2Fisheries Research Services, Marine Laboratory, Aberdeen,
92.8% identical to Cuban and Australian strain sequences, respectively.                 UNITED KINGDOM.
To our knowledge, this work represents the first report of Bm86 sequence
analysis from an Asian strain of B. microplus. Bm86 divergence among             CpG oligodeoxynucleotides (CpG ODN) show promise as
Thai and other B. microplus strains suggests that further work is            immunostimmulatory agents and vaccine adjuvants in animal models.
warranted to determine if a geographic strain-specific vaccine would be      CpG ODN were tested for their capacity to stimulate bactericidal ability
more effective in Thailand.                                                  and respiratory burst activity in rainbow trout (Oncorhynchus mykiss)
                                                                             head kidney (HK) leucocytes. Their ability to stimulate type 1
References:                                                                  interferon production was investigated using a stable RTG-2 cell line
1. Willadsen P, Bird PE, Cobon GS, et al. Commercialization of a             transfected with a luciferase reporter vector and the rainbow trout Mx
   recombinant vaccine against Boophilus microplus. Parasitol 1995;          promoter. Their capacity to enhance protection against bacterial
   110: S43-S50                                                              challenge alone and as an adjuvant was determined. These studies
2. Rand KN, Moor T, Sriskantha A, et al. Cloning and expression of a         revealed different ODN acted in different ways with ODN 2133
   protective antigen from the cattle tick Boophilus microplus. Proc.        inducing significantly (p<0.05 by one way ANOVA, Tukey’s pairwise
   Natl. Acad. Sci. USA 1989; 86: 9657-9661                                  comparison) more bactericidal activity and luciferase production than
                                                                             seen in the cells incubated in medium alone or with ODN 2143.
                                                                             Supernatant from HK leucocytes incubated with ODN 2133 also
          Intranasal Vaccination of Mares to Protect Against Streptococcal   significantly enhanced luciferase production providing evidence that the
P74       Uterine Infections
          R. C. Causey
                                                                             Mx promoter is activated indirectly. Conversely, ODN 2143
                                                                             significantly inhibited the ability of Poly I:C to activate the Mx
          Animal and Veterinary Sciences, University of Maine, Orono, ME.    promoter and significantly reduced the respiratory burst in HK
                                                                             macrophages in response to PMA. ODN 2143 did however,
    Background: Intranasal Salmonella vectors show promise in                significantly enhance protection against bacterial challenge when fish
stimulating immunity to streptococcal pathogens at mucosal sites. An         were injected with CpG alone (p<0.001 Peto test) or as an adjuvant to a
attenuated strain of Salmonella enteritica serotype typhimurium              commercially available vaccine (p< 0.05). These results suggest that
expressing the protective protein of Streptococcus zooepidemicus Moore       CpG ODN are capable of upregulating antibacterial systems, enhancing
and Bryans serovar 9 (SzP-MB9) was used to explore the feasibility of        protection against bacterial challenge and inducing early, nonspecific
using intranasal Salmonella vectors to boost equine uterine immunity         antiviral protection in fish but that these responses are sequence specific.
against streptococci. Methods: Ten mares were randomly assigned into
vaccinated and non-vaccinated groups. Mares in the vaccinated group          Reference:
received 2 doses, 2 weeks apart, of 2.5 X 109 CFU of live intranasal         1. Jørgensen JB, Johansen L-H, Steiro K, Johansen A. CpG DNA
vaccine. Serum, nasal and uterine washings and Salmonella cultures were         Induces Protective Antiviral Immune Responses in Atlantic Salmon
collected from both groups before and after vaccination. Immune                 (Salmo salar L.). Journal of Virology 2003; 77:11471-11479.
responses to lipopolysaccharide (LPS) of S typhimurium and purified
recombinant SzP-MB9 were assessed by Enzyme-Linked-
Immunosorbent-Assay (ELISA). Immune responses were detected using
                                                                                       Summary of the Research of Recombinant HEV Vaccine
anti-equine IgA, IgG and protein-G horseradish peroxidase conjugates.
Ortho-phenylene-diamine (OPD) was used as substrate for color
development. Optical density was measured by spectrophotometer, and
                                                                             P76       J. Lin
                                                                                       Lanzhou Institute of Biological Products, Gansu, CHINA
results analyzed by one-way, analysis of variance. Results: Salmonella
was not recovered from any horses post vaccination, and vaccinated               Background: Open reading frame (ORF-2) of the China strain of
horses remained normal on physical examination. Significant (P < 0.05)       hepatitis E virus ’s capsid protein gene (5816~7128nt;224~660aa) was
responses were seen post vaccination to LPS in serum, nasal and uterine      expressed in E. Coli, a protein with a molecular mass of approximately
washings. Significant anti-SzP-MB9 IgA responses were seen in nasal          54kDa was derived from and the purification technics of the expressed
washings of vaccinated animals, but not in serum or uterine washings.        protein was established .After having gained a great deal of purified
Pre-existing levels of antibodies to SzP-MB9 were high in serum of all       pathogen, we produced HEV vaccine and carried out the test of security,
vaccinated horses. Conclusions: These data confirm that intranasal           immunogenicity and protection efficacy against the challenge of HEV
vaccination with attenuated S typhimurium may safely stimulate nasal         ect, all got the satisfied results. Method: To evaluate the
and uterine immune responses in horses. However, pre-existing                immunogenicity and protective efficacy of the recombinant HEV
antibodies may have affected responses to SzP-MB9.                           vaccine, we vaccinated several groups of Rhesus monkeys with the
                                                                             recombinant vaccine and challenged them with a homologous wild-type
References:                                                                  hepatitis E virus. Neither of the immunized animals showed any
1. Sheoran AS, Timoney JF, Tinge SA, et al. Intranasal immunogenicity        elevation of alanine aminotransferase activity after intravenous challenge
   of a _cya _crp-pabA mutant of Salmonella enterica serotype                with wild-type HEV stool isolate, in marked contrast with the
   Typhimurium for the horse. Vaccine 2001;19:3591-3599.                     unimmunized (control) cynos. Microscopic examination of liver biopsy
2. Sirard JC, Niedergang F, Kraehenbuhl JP. Live attenuated Salmonella:      specimens from these immunized cyno failed to detect histopathologic
   a paradigm of mucosal vaccines. Immunol Rev 1999;171:5-26                 evidence of viral hepatitis. All primates which were vaccinated thrice

 92
   on Vaccine Research
                        ABSTRACTS OF SUBMITTED POSTER PRESENTATIONS
with the recombinant protein were protected from hepatitis when they
were challenged with very high doses of the homologous strain of HEV.
The immune process was three times injection in 0, 2, 4 weeks. Primates
vaccinated thrice with a 40µg dose of the recombinant vaccine
formulated with Aluminium Hydroxide Gel adjuvant gave high and
equivalent levels of antibody and were completely protected from
hepatitis after challenge with wild-type hepatitis E virus .
Results: The results indicated that the rhesus immunized by
prokaryotic expressed recombinant HEV structural protein could
effectively defend wild HEV virus attacking.




                                                                          (continued)


                                                                                 93
          Eighth Annual Conference
                                                                         AUTHOR INDEX
Author                    Presentation Number                   Bellone, C. . . . . . . . . . . . . . . . . . . . . .P12      Chou, T. . . . . . . . . . . . . . . . . . . . . . . .P48
                                                                Author                    Presentation Number                 Author                     Presentation Number
Aaberge, I. . . . . . . . . . . . . . . . . .P50, P51
Aase, A. . . . . . . . . . . . . . . . . . . . . . . .P50       Belshe, R. . . . . . . . . . . . . . . . . . . . . . .P12     Chowdhury, M. . . . . . . . . . . . . . . . . .P32

Acevedo, J.       . . . . . . . . . . . . . . . . . . . . .S1   Berg, M. . . . . . . . . . . . . . . . . . . . . . . .P38     Chuprinina, R. . . . . . . . . . . . . . . . . . .S10

Ahlers, N. . . . . . . . . . . . . . . . . . . . . . . .S4      Berger, S. . . . . . . . . . . . . . . . . . . . . . .S15     Cisar, J. O. . . . . . . . . . . . . . . . . . . . . .P24

Ahmed, T. . . . . . . . . . . . . . . . . . . . . .P32          Bethony, J. . . . . . . . . . . . . . . . . . . .S7, S8       Clemens, J. . . . . . . . . . . . . . . . . . . . . .P32

Alexander, J. . . . . . . . . . . . . . . . . . . . .S16        Bhattacharyya, S. . . . . . . . . . . . . . . . .S17          Clymer, J. . . . . . . . . . . . . . . . . . . . . . . .18

Alexander, N. . . . . . . . . . . . . . . . . . . . .S8         Billingsley, S. . . . . . . . . . . . . . . . . . . .P63      Cohen, S. . . . . . . . . . . . . . . . . . . . . . .P46

Anand, S. . . . . . . . . . . . . . . . . . . . . . .P70        Bilsel, P. . . . . . . . . . . . . . . . . . . . . . . .S16   Collet, B. . . . . . . . . . . . . . . . . . . . . . .P75

Aparin, P. . . . . . . . . . . . . . . . . . . . . . .S10       Biragyn, A. . . . . . . . . . . . . . . . . . . . . . .S5     Cook, J. . . . . . . . . . . . . . . . . . . . . . . .P46

Apelian, D. . . . . . . . . . . . . . . . . . . . . .P56        Bishop, R. . . . . . . . . . . . . . . . . . . . . .P45       Cope, L. . . . . . . . . . . . . . . . . . . . . . . .P46

Arimoto, Y. . . . . . . . . . . . . . . . . . . . .P62          Blackwelder, W. . . . . . . . . . . . . . . . . .S11          Cordeiro-da-Silva . . . . . . . . . . . . . . . .P47

Arroyo, J. . . . . . . . . . . . . . . . . . . . . . .P63       Borrow, R. . . . . . . . . . . . . . . . . . . . . .P15       Costantino, P. . . . . . . . . . . . . . . . . . . .P51

Arsenault, G. . . . . . . . . . . . . . . . . . . .S13          Bottazzi, M. . . . . . . . . . . . . . . . . . .S7, S8        Crowe, J. . . . . . . . . . . . . . . . . . . . . . . .28

Assadou, M. . . . . . . . . . . . . . . . . . . . .S12          Boulianne, N. . . . . . . . . . . . . . . . . . . .P11        Cuberos, L. . . . . . . . . . . . . . . . . . . . .P31

Atmar R. . . . . . . . . . . . . . . . . . . . . . . . .8       Bray, M. D. . . . . . . . . . . . . . . . . . . . .S17        Cutts F. . . . . . . . . . . . . . . . . . . . . . . . . . .5

Azimpour, C. . . . . . . . . . . . . . . . . . . .P34           Breiman, R. . . . . . . . . . . . . . . . . . . . .P32        Cyr, S. . . . . . . . . . . . . . . . . . . . . . . . .P49

Baatar, D. . . . . . . . . . . . . . . . . . . . . . . .S5      Brooker, S. . . . . . . . . . . . . . . . . . . .S7, S8       Daigneault, J. . . . . . . . . . . . . . . . . . . .S13

Baby, M. . . . . . . . . . . . . . . . . . . . . . . .S12       Brunham, R. . . . . . . . . . . . . . . . . . . .S15          Dalloul, R. . . . . . . . . . . . . . . . . . . . . .S20

Bachmann, M. . . . . . . . . . . . . . . . . . . .P6            Buller, M. . . . . . . . . . . . . . . . . . . . . . .P12     Daly, P. . . . . . . . . . . . . . . . . . . . . . . . .S13

Badger, C. . . . . . . . . . . . . . . . . . . . . .P16         Burkhard, P. . . . . . . . . . . . . . . . . . . . . .P6      de Roux, A. . . . . . . . . . . . . . . . . . . . . .S4

Bagayogo, M. . . . . . . . . . . . . . . . . . . .P31           Burt, D. . . . . . . . . . . . . . . . . . . . . . . .P49     Decker, M. . . . . . . . . . . . . . . . . . . . . .S18

Ballou, R. . . . . . . . . . . . . . . . . . . . . . . .21      Bush, G. . . . . . . . . . . . . . . . . . . . . . . .P16     Del Giudice, G. . . . . . . . . . . . . . . . . . .11

Bansal, A. . . . . . . . . . . . . . . . . . . . . . .P46       Bystricky, S. . . . . . . . . . . . . . . . . . . . .P41      dela Cruz, T. . . . . . . . . . . . . . . . . . . . .P64

Barman, S. . . . . . . . . . . . . . . . . . . . . .P60         Campbell, J. . . . . . . . . . . . . . . . . . . . .P26       Dhiman, N. . . . . . . . . . . . . . . . . . . . .S23

Barnoy, S. . . . . . . . . . . . . . . . . . . . . . .P39       Cao, H. . . . . . . . . . . . . . . . . . . . . . . .S14      Diallo, D. . . . . . . . . . . . . . . . . . .S12, P26

Barrett, A. . . . . . . . . . . . . . . . . . . . . . .14       Capps, W. . . . . . . . . . . . . . . . . . . . . .P16        Diaz-Mitoma, F. . . . . . . . . . . . . . .S2, P36

Barry, E. . . . . . . . . . . . . . . . . . . . . . . .S11      Carbone, K. . . . . . . . . . . . . . . . . . . . .S24        Dicko, A. . . . . . . . . . . . . . . . . . . . . . .S12

Bastien, N. . . . . . . . . . . . . . . . . . . . . .S15        Carrington, A. . . . . . . . . . . . . . . . . . .P75         Diemert, D. . . . . . . . . . . . . . . . . . . . .S12

Baxendale, D. . . . . . . . . . . . . . . . . . . .S18          Carter, D. . . . . . . . . . . . . . . . . . . . . . . .P7    DiMiceli, L. . . . . . . . . . . . . . . . . . . . .P61

Becker, P. . . . . . . . . . . . . . . . . . . . . . .P34       Caugant, D. . . . . . . . . . . . . . . . .P50, P51           Ding, X. . . . . . . . . . . . . . . . . . . . . . . .S20

Begum, Y. . . . . . . . . . . . . . . . . . . . . . .P32        Causey, R. . . . . . . . . . . . . . . . . . . . . .P74       Dion, R. . . . . . . . . . . . . . . . . . . . . . . .P11

Bekan, B. . . . . . . . . . . . . . . . . . . . . . .P27        Chabot, S. . . . . . . . . . . . . . . . . . . . . .P49       Dionne, M. . . . . . . . . . . . . . . . . .S2, P30

Bell, S. . . . . . . . . . . . . . . . . . . . . . . . .P63     Cheng, S. . . . . . . . . . . . . . . . . . . . . . .P23      Doherty, C. . . . . . . . . . . . . . . . . . . . . .P8

Bellgrau, D. . . . . . . . . . . . . . . . . . . . .P56         Choi, J. . . . . . . . . . . . . . . . . . . .P13, P18        Dolo, A. . . . . . . . . . . . . . . . . . . . . . . .S12



94
   on Vaccine Research
                                                                          AUTHOR INDEX
Author                     Presentation Number                  Author                    Presentation Number                  Author                    Presentation Number

Doumbia, M. . . . . . . . . . . . . . . . . . . .P31            Galanis, E. . . . . . . . . . . . . . . . . . . . . .S13       Hogan, R. . . . . . . . . . . . . . . . . . . . . .P16
Doumbo, O. . . . . . . . . . . . . . . . . . . .S12             Gantcho, T. . . . . . . . . . . . . . . . . . . . .S10         Høiby, E. . . . . . . . . . . . . . . . . . . . . . .P50
Doustdari, F. . . . . . . . . . . . . . . . . . . .P67          García-Sastre, A. . . . . . . . . . . . . . . . . .S14         Holst, J. . . . . . . . . . . . . . . . . . . . . . . .P51
Dowling, W. . . . . . . . . . . . . . . . . . . . .P16          Gaudreau, M. . . . . . . . . . . . . . . . . . . .P43          Honjo, A. . . . . . . . . . . . . . . . . . . . . . .P62
Du, X. . . . . . . . . . . . . . . . . . . . . . . . . .S6      Geiger S . . . . . . . . . . . . . . . . . . . . . . . .S8     Honko, A. N. . . . . . . . . . . . . . . . . . . . .P2
Dubovsky, F. . . . . . . . . . . . . . . . . . . . . .19        George, H. . . . . . . . . . . . . . . . . . . . . .P46        Hooper J . . . . . . . . . . . . . . . . . . . . . .S21
Duarte-Monteiro . . . . . . . . . . . . . . . .P28              Giardina, P. . . . . . . . . . . . . . . . . . . . .P15        Hotez, P. . . . . . . . . . . . . . . . . . . . . .S7, S8
Duke, R. . . . . . . . . . . . . . . . . . . . . . .P56         Gilca, V. . . . . . . . . . . . . . . . . . . . . . . .P11     Houghton, M. . . . . . . . . . . . . . . . . . . .24
Duncan, R. . . . . . . . . . . . . . . . . . . . .P68           Goldblatt D. . . . . . . . . . . . . . . . . . . . . . .3      Hu, A. . . . . . . . . . . . . . . . . . . . . . . . .P23
Dunning, A. . . . . . . . . . . . . . . . . . . . . .P4         Golovina, M. . . . . . . . . . . . . . . . . . . .S10          Hu, R. . . . . . . . . . . . . . . . . . . . . . . . .P40
Duval, B. . . . . . . . . . . . . . . . . . .P11, P36           Gordon, G. . . . . . . . . . . . . . . . . . . . .P56          Huang, X. . . . . . . . . . . . . . . . . . . . . . .S14
Ebensen, T. . . . . . . . . . . . . . . . . . . . . .P34        Goshima, T. . . . . . . . . . . . . . . . . . . . .P62         Hussell, T. . . . . . . . . . . . . . . . . . . . . . .29
Edwards, S. . . . . . . . . . . . . . . . . . . . . .P4         Goud, G. . . . . . . . . . . . . . . . . . . . . . . .S7       Hutt, P. . . . . . . . . . . . . . . . . . . . . . . . .P8
El-Ghazali, N. . . . . . . . . . . . . . . . . . .P69           Graff, A. . . . . . . . . . . . . . . . . . . . . . . . .P6    Ibrahim, S. . . . . . . . . . . . . . . . . . . . . .P69
Elias, F. . . . . . . . . . . . . . . . . . . . . . . . . .P5   Grey, L. . . . . . . . . . . . . . . . . . . . . . . .P16      Inoue, S. . . . . . . . . . . . . . . . . . . . . . . .P65
Elkina, S. . . . . . . . . . . . . . . . . . . . . . .S10       Gruber,W. . . . . . . . . . . . . . . . . . . . . . .S4        Insel, R. . . . . . . . . . . . . . . . . . . . . . . . .26
Elrick, D. . . . . . . . . . . . . . . . . . . . . . .P36       Guasparini, R. . . . . . . . . . . . . . . . . . . .S2         Iskander, J. . . . . . . . . . . . . . . . . . . . . .P61
Emery, D. . . . . . . . . . . . . . . . . .P42, P66             Guindo, O. . . . . . . . . . . . . . . . . . . . .S12          Jacobsen, S. . . . . . . . . . . . . . . . . . . . .S23
Falgout, B. . . . . . . . . . . . . . . . . . . . . .P38        Guttieri M . . . . . . . . . . . . . . . . . . . . .S21        Jacobson, R. . . . . . . . . . . . . . . . .S22, S23
Fan, H. . . . . . . . . . . . . . . . . . . . . . . . .P46      Guzman, C. . . . . . . . . . . . . . . . . . . . .P34          Jansen, K. . . . . . . . . . . . . . . . . . . . . . .P46
Faruque, S. . . . . . . . . . . . . . . . . . . . . .P32        Hall, A. . . . . . . . . . . . . . . . . . . . . . . . .P8     Jechlinger, W. . . . . . . . . . . . . . . . . . . .P34
Feiring, B. . . . . . . . . . . . . . . . . . . . . .P51        Haller, A. . . . . . . . . . . . . . . . . . . . . . .P56      Jefferies, D. . . . . . . . . . . . . . . . . . . . . .P8
Fernsten, P. . . . . . . . . . . . . . . . . .P14, P15          Halperin, S. . . . . .S2, S18, P28, P30, P36                   Jin, H. . . . . . . . . . . . . . . . . . . . . . . . . .P3
Ferro, S. . . . . . . . . . . . . . . . . . . . . . . .P30      Haran, J. . . . . . . . . . . . . . . . . . . . . . .S14       Jittapalapong, S. . . . . . . . . . . . . . . . . .P73
Finlay, B. . . . . . . . . . . . . . . . . . . . . . .S19       Hardy, C. . . . . . . . . . . . . . . . . . . . . . .P72       Johnson, D. . . . . . . . . . . . . . . . . . . . . .17
Fletcher, P. . . . . . . . . . . . . . . . . . . . . . .P4      Harris, S. . . . . . . . . . . . . . . . . . . . . . .P14      Jones, T. . . . . . . . . . . . . . . . . . . . . . . .P49
Flo, J. . . . . . . . . . . . . . . . . . . . . . . . . . .P5   Hartwell, E. . . . . . . . . . . . . . . . . . . . .P57        Joyce, J. . . . . . . . . . . . . . . . . . . . . . . .P46
Franzusoff, A. . . . . . . . . . . . . . . . . . . .P56         Hayney, M. . . . . . . . . . . . . . . . . .P9, P10            Kaewmongkol, K. . . . . . . . . . . . . . . .P73
French, N. . . . . . . . . . . . . . . . . . . . . .P72         Heckert, R. . . . . . . . . . . . . . . . . . . . . .S20       Kaliraj, P. . . . . . . . . . . . . . . . . . . . . . .P70
Frey, S. . . . . . . . . . . . . . . . . . . . . . . . .P12     Hepler, R. . . . . . . . . . . . . . . . . . . . . .P46        Kallos, A. . . . . . . . . . . . . . . . . . . . . . .P29
Fritzsønn, E. . . . . . . . . . . . . . . . . . . . .P50        Heppner, D. . . . . . . . . . . . . . . . . . . . . .22        Kamate, B. . . . . . . . . . . . . . . . . . . . . .S12
Frolushkina, T. . . . . . . . . . . . . . . . . . .S10          Heymann D. . . . . . . . . . . . . . . . . . . . . .1          Kamau, L. . . . . . . . . . . . . . . . . . . . . .P45
Fulford, T. . . . . . . . . . . . . . . . . . . . . . .P8       Higgins, D. . . . . . . . . . . . . . . . . . . . .P64         Kang, C. . . . . . . . . . . . . . . . . . . . . . . .P18
Gahan, M. . . . . . . . . . . . . . . . . . . . . .S19          Hill, R. . . . . . . . . . . . . . . . . . . . . . . . . .15   Kang, Y. . . . . . . . . . . . . . . . . . . . . . . . .P3



                                                                                                                                                                                       95
          Eighth Annual Conference
                                                                        AUTHOR INDEX
Author                    Presentation Number                 Author                     Presentation Number                  Author                    Presentation Number

Kappe, S. . . . . . . . . . . . . . . . . . . . . . . .20     Law, B. . . . . . . . . . . . . . . . . . . . . .S2, P36        Mandl, C. . . . . . . . . . . . . . . . . . . . . .P20
Karim, A. . . . . . . . . . . . . . . . . . . . . . .P69      Lawrence, S. . . . . . . . . . . . . . . . . . . . .P12         Marsh, B. . . . . . . . . . . . . . . . . . . . . . .P71
Kast, W. . . . . . . . . . . . . . . . . . . . . . . . .23    Lee, S. . . . . . . . . . . . . . . . . . . . . . . . .P18      Marty, K. . . . . . . . . . . . . . . . . . . . . . .P29
Kato, T. . . . . . . . . . . . . . . . . . . . . . . .P62     Leeper, A. . . . . . . . . . . . . . . . . . . . . . . .P4      Matsuda, T. . . . . . . . . . . . . . . . . . . . .P35
Katsuta, T. . . . . . . . . . . . . . . . . . . . . .P62      Lees, A. . . . . . . . . . . . . . . . .P52, P53, S1            Matsumoto, T. . . . . . . . . . . . . . . . . . .P35
Katz, J. . . . . . . . . . . . . . . . . . . . . . . . .S16   Leffel, E. . . . . . . . . . . . . . . . . . . . . . .P46       Matsushima, K. . . . . . . . . . . . . . . . . .P65
Keller, P. . . . . . . . . . . . . . . . . . . . . . . .P46   Levine, M. . . . . . . . . . . . . .S11, P26, P31               Maus, D. . . . . . . . . . . . . . . . . . . . . . .S18
Kelly, R. . . . . . . . . . . . . . . . . . . . . . . .P46    Li, C. . . . . . . . . . . . . . . . . . . . . . . . . . .P7    Mbawuike, I. . . . . . . . . . . . . . . . . . . .P64
Kemmler, C. . . . . . . . . . . . . . . . . . . . .P56        Li, F. . . . . . . . . . . . . . . . . . . . . . . . . . .P23   Mboujka, I. . . . . . . . . . . . . . . . . . . . .S14
Ketner, G. . . . . . . . . . . . . . . . . . . . . .P38       Li, H. . . . . . . . . . . . . . . . . . . . . . . . . .P40     McCaughey, M. . . . . . . . . . . . . . . . . . .P4
Kidokoro, M. . . . . . . . . . . . . . . . . . . .P65         Li, L. . . . . . . . . . . . . . . . . . . . . . . . . .P17     McConkey, S. . . . . . . . . . . . . . . . . . . . .P8
Killeen, K. . . . . . . . . . . . . . . . . . . . . .P32      Li, Y. . . . . . . . . . . . . . . . . . . . . . . . . . .S15   McElroy A. . . . . . . . . . . . . . . . . . . . . .S21
King, A. . . . . . . . . . . . . . . . . . . . . . . .S15     Libraty, D. . . . . . . . . . . . . . . . . . . . . .P60        McNeely, T. . . . . . . . . . . . . . . . . . . . .P46
King, T. . . . . . . . . . . . . . . . . . . . . . . .P56     Lillehoj, E. . . . . . . . . . . . . . . . . . . . . .S20       McNeil, S. . . . . . . . . . . . . . . . . . . . . .P30
Kirithika, K. . . . . . . . . . . . . . . . . . . . .P70      Lillehoj, H. . . . . . . . . . . . . . . . . . . . . .S20       Medhat, A. . . . . . . . . . . . . . . . . . . . . .P69
Kitabatake, M. . . . . . . . . . . . . . . . . . .P65         Lin, J. . . . . . . . . . . . . . . . . . . . . . . . . .P76    Meekison, W. . . . . . . . . . . . . . . . . . . .P30
Klein, J. . . . . . . . . . . . . . . . . . . . . . . . .16   Liu, J. . . . . . . . . . . . . . . . . . . . . . . . . .P17    Mekalanos, J. . . . . . . . . . . . . . . . . . . .P32
Klinman, D. . . . . . . . . . . . . . . . . . . . .S20        Locher, C. . . . . . . . . . . . . . . . . . . . . . .33        Meloff, K. . . . . . . . . . . . . . . . . . . . . .P28
Klugman K. . . . . . . . . . . . . . . . . . . . . . .2       Lockhart, S. . . . . . . . . . . . . . . . . . . . . .P4        Mendez, S. . . . . . . . . . . . . . . . . . . . . . .S7
Koehm, S. . . . . . . . . . . . . . . . . . . . . .P12        Lode, H. . . . . . . . . . . . . . . . . . . . . . . . .S4      Mendy, M. . . . . . . . . . . . . . . . . . . . . . .P8
Kofler, R. . . . . . . . . . . . . . . . . . . . . . .P20     Long, C. . . . . . . . . . . . . . . . . . . . . . . .S12       Meyer Næss, L. . . . . . . . . . . . . . . . . .P51
Kohara, M. . . . . . . . . . . . . . . . . . . . . .P65       Longworth, E. . . . . . . . . . . . . . . . . . .P15            Michalek S. . . . . . . . . . . . . . . . . . . . . .10
KoKai-kun, J. . . . . . . . . . . . . . . . . . . . .S1       Lopez, R. . . . . . . . . . . . . . . . . . . . . . . .P5       Miller E. . . . . . . . . . . . . . . . . . . . . . . . . .4
Kopecko, D. J. . . . . . . . . . . . . . .P24, S17            Lopez A. . . . . . . . . . . . . . . . . . . . .P53, S1         Miller, L. . . . . . . . . . . . . . . . . . . . . . .S12
Kotloff, K. . . . . . . . . . . .9, S11, P26, P31,            Losada, M. . . . . . . . . . . . . . . . . . . . . .P46         Mills, E. . . . . . . . . . . . . . . . . . . . .S2, P30
Kristiansen, P. . . . . . . . . . . . . . .P50, P51           Lottenbach, K. . . . . . . . . . . . . . . . . . .P12           Min, W. . . . . . . . . . . . . . . . . . . . . . . .S20
Kurbatova, I. Yu. . . . . . . . . . . . . . . . .S10          Loukas, A. . . . . . . . . . . . . . . . . . . . . . .S7        Mitchell, A. . . . . . . . . . . . . . . . . . . . .P63
Kurtz, M. . . . . . . . . . . . . . . . . . . . . . .P46      Lu, S. . . . . . . . . . . . . . . . . . . . . .P48, S14        Mizel, S. . . . . . . . . . . . . . . . . . . . . . . . .P2
Lacasse, P. . . . . . . . . . . . . . . . . . . . . . .P43    Lu, Y. . . . . . . . . . . . . . . . . . . . . . . . . .P56     Mizuno, K. . . . . . . . . . . . . . . . . . . . . .P65
LaJeunesse, C. . . . . . . . . . . . . . . . . . .P29         Lubitz, W. . . . . . . . . . . . . . . . . . . . . .P34         Monath, T. . . . . . . . . . . . . . . . . . . . . . .34
Langley, J. . . . . . . . . . . . . . . . . . .S2, P30        Lvov, V. L. . . . . . . . . . . . . . . . . . . . . .S10        Mond, J. . . . . . . . . . . . . . . . . . . . . . . . .S1
Lanzavecchia, A. . . . . . . . . . . . . . . . . . .30        Ma, W. . . . . . . . . . . . . . . . . . . . . . . . .P17       Montaner, A. . . . . . . . . . . . . . . . . . . . .P5
Larder, A. . . . . . . . . . . . . . . . . . . . . . .S15     Machaidze, G. . . . . . . . . . . . . . . . . . . .P6           Moon, H. . . . . . . . . . . . . . . . . . . . . . .P18
Lavigne, P. . . . . . . . . . . . . . . . . . . . . .S18      Malkin, E. . . . . . . . . . . . . . . . . . . . . .S12         Morcol, T. . . . . . . . . . . . . . . . . . . . . .P63



96
on Vaccine Research
                                                                   AUTHOR INDEX
Author                   Presentation Number                 Author                   Presentation Number                 Author                    Presentation Number

Morita, K. . . . . . . . . . . . . . . . . . . . . .P65      Pitt, M. . . . . . . . . . . . . . . . . . . . . . . .P46    Sakhatskyy, P. . . . . . . . . . . . . . . . . . . .P48
Mozel, M. . . . . . . . . . . . . . . . . . . . . .P29       Plumb, G. . . . . . . . . . . . . . . . . . . . . .P71       Salam, M. . . . . . . . . . . . . . . . . . . . . . .P32
Mullen, G. . . . . . . . . . . . . . . . . . . . . .S12      Poland, G. . . . . . . . . . . . . . . . . .S22, S23         Salotra, P. . . . . . . . . . . . . . . . . . . . . . .P68
Murai, F. . . . . . . . . . . . . . . . . . . . . . .P65     Pool, V. . . . . . . . . . . . . . . . . . . . . . . .P61    Sasaki, S. . . . . . . . . . . . . . . . . . . . . . .P35
Murugan, V. . . . . . . . . . . . . . . . . . . . .P70       Predy, G. . . . . . . . . . . . . . . . . . . .S2, P30       Sauder, C. . . . . . . . . . . . . . . . . . . . . . .S24
Musoke, T. . . . . . . . . . . . . . . . . . . . . .P45      Promkhatkaew, D. . . . . . . . . . . . . . . .P55            Saul, A. . . . . . . . . . . . . . . . . . . . . . . . .S12
Nagaoka, C. . . . . . . . . . . . . . . . . . . . .P62       Protodiakonov, A. . . . . . . . . . . . . . . . .S10         Scheifele, D. . . . . . . . . . . . . . . . .P28, P29
Nagappan, P. . . . . . . . . . . . . . . . . . . .P63        Qadri, F. . . . . . . . . . . . . . . . . . . . .P32, S9     Schellekens, C. . . . . . . . . . . . . . . . . . . .P6
Nakajima, N. . . . . . . . . . . . . . . . . . . .P62        Rafati, S. . . . . . . . . . . . . . . . . . . . . . .P67    Schenk, D. . . . . . . . . . . . . . . . . . . . . . .25
Nakhaee, A. . . . . . . . . . . . . . . . . . . . .P67       Raman, S. . . . . . . . . . . . . . . . . . . . . . . .P6    Schiavo, R. . . . . . . . . . . . . . . . . . . . . . .S5
Nakhasi, H. . . . . . . . . . . . . . . . . . . . .P68       Rames, J. . . . . . . . . . . . . . . . . . . . . . .P25     Schmaljohn, C. . . . . . . . . . . . . .P16, S21
Narayanan, P. . . . . . . . . . . . . . . . . . . .P19       Ranallo, R. . . . . . . . . . . . . . . . . . . . . .P39     Schmoele-Thoma . . . . . . . . . . . . . . . . .S4
Nataro, J. . . . . . . . . . . . . . . . . . . . . . .S11    Rangarajan, P. . . . . . . . . . . . . . . . . . . .P33      Schultz, L. . . . . . . . . . . . . . . . . . . . . .P46
Neatby, A. . . . . . . . . . . . . . . . . . . . . .S18      Rappaport, R. . . . . . . . . . . . . . . . . . .P23         Secombes, C. . . . . . . . . . . . . . . . . . . .P75
Nerenbaum, L. . . . . . . . . . . . . . . . . . .P63         Rappuoli, R. . . . . . . . . . . . . . . . . . . . .P51      Seidlein, L. . . . . . . . . . . . . . . . . . . . . .P32
Newman, F. . . . . . . . . . . . . . . . . . . . .P12        Rayco-Solon, P. . . . . . . . . . . . . . . . . . .P8        Selvapandiyan, A . . . . . . . . . . . . . . . .P68
Newman, M. . . . . . . . . . . . . . . . . . . .S16          Reddy, M. . . . . . . . . . . . . . . . . . . . . .P70       Sen, S. . . . . . . . . . . . . . . . . . . . . . . . .P57
Niambele, M. . . . . . . . . . . . . . . . . . . .S12        Remple, V. . . . . . . . . . . . . . . . . . . . . .S13      Seong, S. . . . . . . . . . . . . . . . . . . . . . .P18
Norheim, G. . . . . . . . . . . . . . . .P50, P51            Reubel, G. . . . . . . . . . . . . . . . . . . . . .P72      Serres, G. De. . . . . . . . . . . . . . . . . . . .P11
Noya, F. . . . . . . . . . . . . . . . . . . . . . . .P30    Robbins J . . . . . . . . . . . . . . . . . . . . . . . .6   Seth, P. . . . . . . . . . . . . . . . . . . . . . . . .P54
Ojah, C. . . . . . . . . . . . . . . . . . . . . . . .P30    Robinson, H. . . . . . . . . . . . . . . . . . . . .31       Shadomy, S. . . . . . . . . . . . . . . . . . . . .P61
Okuda, K. . . . . . . . . . . . . . . . . . . . . .P35       Rodell, T. . . . . . . . . . . . . . . . . . . . . . .P56    Shafer, D. . . . . . . . . . . . . . . . . . . . . . .P52
Osorio, M. . . . . . . . . . . . . . . . . . . . . .S17      Rodrigues, L. . . . . . . . . . . . . . . . . . . . .S8      Shi, R. . . . . . . . . . . . . . . . . . . . . . . . .P17
Osterhaus, A. . . . . . . . . . . . . . . . . . . . .12      Rodriguez, J. . . . . . . . . . . . . . . . . . . . .P5      Shida, H. . . . . . . . . . . . . . . . . . . . . . .P65
Ott, G. . . . . . . . . . . . . . . . . . . . . . . .P64     Rosenqvist, E. . . . . . . . . . . . . . .P50, P51           Shiver, J. . . . . . . . . . . . . . . . . . . . . . . . .32
Ouaissi, A. . . . . . . . . . . . . . . . . . . . . .P47     Roser, B. . . . . . . . . . . . . . . . . . . . . . . .P57   Shmigol, V. . . . . . . . . . . . . . . . . . . . . .S10
Ovsyannikova, I. . . . . . . . . . . . .S22, S23             Rowlands, J. . . . . . . . . . . . . . . . . . . . .P45      Shurtleft, A. . . . . . . . . . . . . . . . . . . . .S21
Owusu-Agyei, S . . . . . . . . . . . . . . . . .P22          Rubin, S. . . . . . . . . . . . . . . . . . . . . . .S24     Siber, G. . . . . . . . . . . . . . . . . . . . . .S4, P4
Pankratz, S. V. . . . . . . . . . . . . . .S22, S23          Ryan, J. . . . . . . . . . . . . . . . . . . . . . . .S23    Siegrist, C. . . . . . . . . . . . . . . . . . . . . . .27
Paragas, J. . . . . . . . . . . . . . . . . . . . . . .P16   Rykers, P. . . . . . . . . . . . . . . . . . . . . . .S18    Sikkema, D. . . . . . . . . . . . . . . . . . .S4, P4
Pasetti, M. . . . . . . . . . . . . . . . . .P31, S11        Sack, D. . . . . . . . . . . . . . . . . . . . .P32, S9      Silveria, I. . . . . . . . . . . . . . . . . . .P58, P59
Pavlova, L. . . . . . . . . . . . . . . . . . . . . .S10     Sagara, I. . . . . . . . . . . . . . . . . . . . . . .S12    Silvestre, R. . . . . . . . . . . . . . . . . . . . .P47
Petric, M. . . . . . . . . . . . . . . . . . . . . . .S15    Saha, A. . . . . . . . . . . . . . . . . . . . . . . .P32    Simon, J. K. . . . . . . . . . . . . . . . . . . . .S11
Pielak, K. . . . . . . . . . . . . . . . . . . . . . .S13    Saha, S. . . . . . . . . . . . . . . . . . . . . . . .P35    Singh, R. . . . . . . . . . . . . . . . . . . . . . .P68



                                                                                                                                                                               97
             Eighth Annual Conference
                                                                          AUTHOR INDEX
Author                    Presentation Number                 Author                   Presentation Number                 Author                    Presentation Number

Sirinarukmitr, T. . . . . . . . . . . . . . . . . .P73        Tapia, M. . . . . . . . . . . . . . . . . . .P26, P31        Welte, T. . . . . . . . . . . . . . . . . . . . . . . . .S4
Sissoko, M. . . . . . . . . . . . . . . . . . . . . .S12      Tapiero, B. . . . . . . . . . . . . . . . . . .S2, P36       Wen, Y. . . . . . . . . . . . . . . . . . . . . .S3, P1
Skilton, R. . . . . . . . . . . . . . . . . . . . . .P45      Taslimi, Y. . . . . . . . . . . . . . . . . . . . . .P67     Wesselingh, S. . . . . . . . . . . . . . . . . . .S19
Skowronski, D. . . . . . . . . . . . . .S13, S15              Tateyama, S. . . . . . . . . . . . . . . . . . . . .P62      Whalen, R. . . . . . . . . . . . . . . . . . . . . . .S6
Skrastina, D. . . . . . . . . . . . . . . . . . . .P44        Thakkar, S. . . . . . . . . . . . . . . . . . . . . .P39     Whitsitt, P. . . . . . . . . . . . . . . . . . . . . . .S2
Smith, B. . . . . . . . . . . . . . . . . . .S18, P28         Thanasilp, S. . . . . . . . . . . . . . . . . . . .P73       Whittle, H. . . . . . . . . . . . . . . . . . . . . .P8
Smith, J. . . . . . . . . . . . . . . . . . . . . . . .P16    Thera, M. . . . . . . . . . . . . . . . . . . . . . .S12     Wiegert, N. . . . . . . . . . . . . . . . . .P9, P10
Sogoba, M. . . . . . . . . . . . . . . . . . . . . .S12       Thompson, E. . . . . . . . . . . . . . . . . . .P16          Wonderling, L. . . . . . . . . . . . . . .P42, P66
Soistman, E. . . . . . . . . . . . . . . . . . . . . .P7      Tissot, A. . . . . . . . . . . . . . . . . . . . . . . .P6   Woods, A. . . . . . . . . . . . . . . . . . . . . .P46
Solórzano, A. . . . . . . . . . . . . . . . . . . .S14        Tokutake, T. . . . . . . . . . . . . . . . . . . . .P62      Wright, J. . . . . . . . . . . . . . . . . . . . . . .P72
Sominskaya, I. . . . . . . . . . . . . . . . . . .P44         Tomovici, A. . . . . . . . . . . . . . . . . . . . . .S2     Wu, Y. . . . . . . . . . . . . . . . . . . . . . . . .S17
Sow, S. . . . . . . . . . . . . . . . . . . . .P26, P31       Tropel, D. . . . . . . . . . . . . . . . . . . . . . .P6     Xu, D. . . . . . . . . . . . . . . . . . . . . .S3, P24
Spik, K. . . . . . . . . . . . . . . . . . . . . . . .S21     Tuck, S. . . . . . . . . . . . . . . . . . . . . . . .P64    Xu, L. . . . . . . . . . . . . . . . . . . . . . . . . . .S6
Sreenivas, G. . . . . . . . . . . . . . . . . . . .P68        Tweed, S. . . . . . . . . . . . . . . . . . .S13, S15        Yamaguchi, K. . . . . . . . . . . . . . . . . . .P35
Srinivasan, V. . . . . . . . . . . . . . . . . . . .P33       van der Sande, M. . . . . . . . . . . . . . . . .P8          Yao, X. . . . . . . . . . . . . . . . . . . . . . . . . .P1
Stanley, S. . . . . . . . . . . . . . . . . . . . . . .P12    Van Nest, G. . . . . . . . . . . . . . . . . . . .P64        Yasui, F. . . . . . . . . . . . . . . . . . . . . . . .P65
Steele, D. . . . . . . . . . . . . . . . . . . . . . . . .7   Vandenburgh, K. . . . . . . . . . . . . . . . .S24           Yuan, Z. . . . . . . . . . . . . . . . . . . . . . . . .S3
Stewart, B. . . . . . . . . . . . . . . . . . . . . .S16      Venkatesan, M. . . . . . . . . . . . . . . . . .P39          Zadeh Vakili, A. . . . . . . . . . . . . . . . . .P67
Stich, R. . . . . . . . . . . . . . . . . . . . . . . .P73    Vierkant, R. . . . . . . . . . . . . . . . .S22, S23         Zahedifard, F. . . . . . . . . . . . . . . . . . . .P67
Stoever, K. . . . . . . . . . . . . . . . . . . .S7, S8       Vivekanandhan, A . . . . . . . . . . . . . . .P19            Zang, G. . . . . . . . . . . . . . . . . . . . . . .P46
Stoica-Popescu . . . . . . . . . . . . . . . . . .P49         Vrati, S. . . . . . . . . . . . . . . . . . . . . . . .P37   Zhan, B. . . . . . . . . . . . . . . . . . . . . . . . .S7
Straub, D. . . . . . . . . . . . . . . . . .P42, P66          Vu Khac, H. . . . . . . . . . . . . . . . . . . . .P21       Zhang, S. . . . . . . . . . . . . . . . . . . . . . .P40
Strive, T. . . . . . . . . . . . . . . . . . . . . . . .P72   Waight, P. . . . . . . . . . . . . . . . . . . . . . . .P8   Zhao, K. . . . . . . . . . . . . . . . . . . . . . . . .S3
Strugnell, R. . . . . . . . . . . . . . . . . . . . .S19      Walker, R. . . . . . . . . . . . . . . . . . . . . .S17      Zhao, P. . . . . . . . . . . . . . . . . . . . . . . .P23
Sujatha, N. . . . . . . . . . . . . . . . . . . . . .P19      Wallenfels, J. . . . . . . . . . . . . . . . . . . .P25      Zheng, W. . . . . . . . . . . . . . . . . . . . . .P17
Swayne, D. . . . . . . . . . . . . . . . . . . . . . .13      Wang, B. . . . . . . . . . . . . . . . . . . . . . . .P3     Zelman, M. . . . . . . . . . . . . . . . . . . . .S18
Sweet, L. . . . . . . . . . . . . . . . . . . . . . . .S18    Wang, S. . . . . . . . . . . . . . . . . . . .P48, S14       Zorzopulos, J. . . . . . . . . . . . . . . . . . . .P5
Sztein, M. . . . . . . . . . . . . . . . . . . . . . .S11     Ward, B. . . . . . . . . . . . . . . . . . . . . . . .P49
Taaffe, J. . . . . . . . . . . . . . . . . . . . . . . .S14   Wasawo, D. . . . . . . . . . . . . . . . . . . . .P45
Taheri, T. . . . . . . . . . . . . . . . . . . . . . .P67     Wasserman, S. . . . . . . . . . . . . . . . . . .S11
Takeshita, F. . . . . . . . . . . . . . . . . . . . .P35      Watson, W. . . . . . . . . . . . . . . . . . . . . . .P4
Talbot, B. . . . . . . . . . . . . . . . . . . . . . .P43     Webster, D. . . . . . . . . . . . . . . . . . . . .S19
Tam, J. . . . . . . . . . . . .S13, S15, P14, P23             Wedege, E. . . . . . . . . . . . . . . . . . . . . .P51
Tangen, T. . . . . . . . . . . . . . . . . . . . . .P50       Wei, X. . . . . . . . . . . . . . . . . . . . . . . . .P46



  98
  on Vaccine Research
                                                  AUTHOR I INDEX
                                                 DISCLOSURENDEX
As a sponsor accredited by the Accreditation Council of Continuing Medical Education (ACCME) the National
Foundation for Infectious Diseases must insure balance, independence, objectivity, and scientific rigor in all its
individually sponsored or jointly sponsored educational activities. All faculty participating in a sponsored activity and all
Scientific Program Committee Members are expected to disclose to the activity audience: (1) any significant financial
interest or other relationship (a) with the manufacturer(s) of any commercial product(s) and/or provider(s) of commercial
services discussed in an educational presentation and and/or (b) with any commercial supporters of the activity.
(Significant financial interest or other relationship can include such things as grants or research support, employee,
consultant, major stock holder, member of speakers bureau, etc.); and (2) any intention to discuss off-label uses of
regulated substances or devices.

The intent of this disclosure is not to prevent a speaker, nor a Scientific Program Committee member, with a significant
financial or other relationship from making a presentation, or assisting in conference organization, but rather to provide
listeners with information on which they can make their own judgments. It remains for the audience to determine
whether the speaker's interests or relationships may influence the presentation with regard to exposition or conclusion.

The following Presenters have no relationships to disclose:
C. Azimpour Tabrizi         V. Gilca                C. LaJeunesse               F. Qadri                 S. Sow
B. Bekan                    E. Hartwell             J. Langley                  S. Rafati                D. Steele
M. Berg                     M. Hayney               S. Lawrence                 R. Ranallo               B. Talbot
A. Biragyn                  A. Honjo                D. Libraty                  G. Reubel                M. Tapia
M. Bottazzi                 A. Honko                J. Lin                      J. Robbins               D. Tropel
S. Bystricky                R. Hu                   S. Lu                       E. Rosenqvist            A. Vivekanandhan
R. Causey                   E. Hwang                S. McNeil                   R. Sadri                 L. Yuexi
J. Choi                     B. Imoukhuede           M. Mendy                    S. Saha                  H. Vu khac
R. Dalloul                  S. Jittapalapong        A. Montaner                 P. Sakhataskyy           S. Vrati
A. de Roux                  T. Kaihua               V. Muzio                    P. Salotra               K. Walia
N. Dhiman                   P. Kaliraj              A. Olagun                   C. Sauder                J. Wallenfels
A. Dicko                    L. Kamau                M. Osorio                   P. Seth                  B. Wang
L. DiMiceli                 C. Kang                 S. Owusu-Agyei              R. Shi                   Y. Wen
W. Dowling                  A. Karim                I. Ovsyannikova             I. Silveria              R. Whalen
M. Ebrahimi                 M. Kitabatake           G. Plumb                    J. Simon                 X. Yao
M. Gahan                    R. Kofler               D. Promkhatkaew             D. Skrastina             D. Xu

The following Program Committee Members have no relationship to disclose:

L. Babiuk      R. Duma        P. Nara     H. Golding        P. McInnes      R. Rabinovich        H. Robinson        C. Schmaljohn


The remaining Presenters have disclosed the following:
Presenter                     Company                                                                    Relationship*
J. Alexander                  Epimmune                                                                   A,C
R. Atmar                      Corixa, Vaxgen                                                             E
J. Crowe                      MedImmune                                                                  A
                              sanofi aventis, MedImmune, Vaxgen                                          B
                              MedImmune, Morphotek, Symphogen, Syngenta, VaxGen, Vaxin                   E
                              sanofi pasteur                                                             G
S. Cyr                        ID Biomedical                                                              A
T. dela Cruz                  Dynavax Technologies                                                       A,C
G. Del Giudice                Chiron                                                                     C
P. Giardina                   Wyeth                                                                      A,C
                                                                                                                     (continued)


                                                                                                                                   99
       Eighth Annual Conference
                                                  AUTHOR I INDEX
                                                 DISCLOSURENDEX
 (Remaining Presenters continued)
 A. Haller                      GlobeImmune                                                             A,C
 S. Halperin                    GlaxoSmithKline                                                         B
 S. Harris                      Wyeth                                                                   C
 R. Hepler                      Merck                                                                   A,C
 D. Heppner                     GlaxoSmithKline                                                         B
 A. Hu                          Wyeth                                                                   A,C
 A. Lees                        Biosynexus, Inc.                                                        A,C,G
 C. Li                          New Century Pharmaceuticals, Inc.                                       A,C
 P. Nagappan                    DynPort Vaccine                                                         B
 P. Rangarajan                  Indian Immunologicals Ltd                                               B
 D. Scheifele                   Wyeth                                                                   B
 G. Siber                       Wyeth                                                                   A,C
 D. Skowronski                  sanofi Pasteur                                                          B
 L. Wonderling                  Syntiron                                                                C

 The remaining Program Committee Members disclosed the following:

 Presenter                      Company                                                                 Relationship*
 C. Baker                       Chiron                                                                  E
 D. Griffin                     Chiron, Vical                                                           Collaboration
                                MedImmune                                                               F
                                Elan, Wyeth                                                             DSMB
 R. Lambert                     Chiron, GlaxoSmithKline, Ortho McNeil                                   E
 M. Levine                      VaxGen                                                                  A
                                GlaxoSmithKline, ID Medical Group                                       B
 S. Plotkin                     sanofi Pasteur                                                          A,C
                                Dynport                                                                 F
 R. Rappuoli                    Chiron                                                                  C
 S. Rehm                        sanofi aventis, Wyeth, Pfizer, Cubist, Glaxo                            E
                                Pfizer                                                                  A
                                Cubist                                                                  B
 A. Shaw                        Merck & Company                                                         C
 G. Siber                       Wyeth Vaccines                                                          A,C
 B. Weniger                     VaxGen                                                                  A

 *Please refer to the following relationship table

   Label         Relationship
  A              I have stocks, stock options, and/or bond holdings in this company
  B              I have a research grant, stipend, and/or fellowship from this company
  C              I am employed by this company, or it employs a member of my immediate family
  D              I or a member of my immediate family own or is a partner in this company
  E              I or a member of my immediate family receive consulting fees, honoraria, paid meeting
                 registration fees, paid travel, speaking fees, or other financial compensation from this company
  F              I or a member of my immediate family hold a nonrenumerative position of influence with this
                 company such as officer, board member, trustee, or public spokesperson.
  G              I or a member of my immediate hold a patent for and/or receive royalties from this company’s product



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