Vaccines

VACCINES AND SERAS IN CLINICAL RESEARCH 7/3/08 1 VACCINES: Microbial preparations of killed or modified microorganisms that can stimulate an immune response in the body to prevent future infections with similar microorganisms. SERA : They are the liquid component of clotted blood. It lacks the formed elements and the clotting factors but retains electrolytes and soluble proteins, including antibodies. Types Of Vaccines Based On Their Action: • Prophylactic vaccines 7/3/08 • Therapeutic vaccines 2 TYPES OF VACCINES: VACCINES CONVENTIONAL VACCINENS PURIFIED ANTIGEN VACCINES RECOMBINANT VACCINES LIVE VACCINES INACTIVATED PATHOGEN RECOMBINANT PROTEINS/ SUBUNIT VACCINES DNA VACCINES WHOLE PROTEIN MOLECULE 7/3/08 POLYPEPTIDE 3 4 VACCINES IN MARKET DISEASE 1) POLIO SABIN SALK VACCINE TYPE OF VACCINE LIVEATTENUATED INACTIVATED DOSE 0.5 ml in mouth 1 ml s.c. in deltoid 2) RABIES PURIFIED CHICK EMBRYO CELL (PCEV) RUBELLA VACCINE MUMPS VIRUS VACCINE MEASLE VACCINE INACTIVATED 1 ml 6 inj. i.m. 3) RUBELLA LIVE ATTENUATED LIVE ATTENUATED LIVE ATTENUATED 1000 TCID 50/0.5 ml Inj. deep s.c./i.m. Single dose of 5000 TCID50 Single dose of 1000 5 TCID50 4) MUMPS 5) MEASLES 7/3/08 Contd… DISEASE 6) TUBERCULOSIS 7) HEPATITIS –B BCG VACCINE TYPE OF VACCINE LIVE ATTENUATED RECOMBINANT DNA SURFACE ANTIGEN LIVE ATTENUATED INACTIVATED DOSE 0.5 ml intracutaneous in deltoid 1 ml in deltoid at 0,1,6 months 0.5 ml s.c. HEPATITIS-B VACCINE TYPHOIDPARATYPHOID A,B (TAB) WHOOPING COUGH VACCINE 8) TYPHOID 9) PERTUSIS 0.25-0.5 ml s.c./i.m. thrice at 4wks interval 0.5 ml deep i.m. 6 10) TETANUS 7/3/08 TETANUS TOXOID LIVE ATTENUATED NATIONAL IMMUNISATION PROGRAMME AGE AT BIRTH VACCINES BCG+OPV(1st DOSE),HEPB(AFT 12-24HRS) DPT+OPV+HEP-B DPT+OPV HEP-B AFTER 6 WKS AFTER 10,14 WKS AT 6th MONTH AT 9th MONTH AT 15-18 MONTHS MEASLES DPT+MMR+OPV(BOOSTER) AT 4-5 YEARS(SCHOOL DTENTRY) DA+OPV(BOOSTER)+TAB AT 10 YEARS TT+TAB AT 16 YEARS TT 7 PHASES OF CLINICAL TRIALS FOR VACCINES • PRECLINICAL STUDIES: Experimental vaccines are first tested in animals for safety and immunogenicity. If results are favourable then it undegoes clinical trials. • Phase I: Introduction of candidate vaccine into human population for determination of its safety and biological effects including immunogenicity. • Phase II: Refers to the initial trials examining effectiveness in a limited number of volunteers. • Phase III: Trials are intended for a more complete assessment of safety and effectiveness in the prevention of disease involving a larger number of volunteers in a multicentre adequately controlled study. • Phase IV: These studies are done to detect the rarer or unexpected events that may not be seen in smaller Phase II/III studies. 7/3/08 8 VACCINE TRIAL PROCESS Goals  Best dose?  Produce an immune response?  Protect after viral challenge? Pre clinical  Safe?  Immune response?  Safe?  How much of an immune response?  Does it work? Phase l Phase II Phase lll Animals 30- 50 People Participants 200 – 400 People 3000 – 5000 People 7/3/08 9 ANTI HIV VACCINE: •The trial is run by Indian Council of Medical Research (ICMR). • The candidate vaccine recombinant Modified Vaccinia Ankara (MVA) being trailed at the National Institute of Epidemiology (NIE) in Chennai. • The vaccine targets HIV-1 subtype C, the most predominant HIV strain in India. • The investigational vaccine candidate TBC-M4 is designed as a preventive vaccine. • The International AIDS Vaccine Initiative (IAVI) and biotechnology firm Therion Biologics Cooperation collaborated on the AIDS vaccine candidate utilizing MVA vector technology. •The Chennai study is a small scale trial, with a primary aim to evaluate the safety of the product. 7/3/08 10 WHERE ARE THESE VACCINES BEING TESTED? 7/3/08 11 ANTI MALARIAL VACCINE: • GlaxoSmithKline’s (GSK) investigational RTS,S/AS02 malaria vaccine in African infants serves as the first proof of concept that the vaccine has a promising safety and tolerability profile and reduces malaria parasite infection. • The primary objective of the study was to assess whether RTS,S could be safely administered to the age group most vulnerable to severe disease and death from malaria. 7/3/08 12 • Phase II trial was conducted by the Manhica Health Research Centre in Mozambique by scientists from the Hospital Clinic of the University of Barcelona and the Mozambique Ministry of Health. The PATH Malaria Vaccine Initiative, is a key partner in the clinical development of RTS,S. • This study helps pave the way for a pivotal Phase III trial of what could be the first malaria vaccine for infants and young children in Africa. • The RTS,S vaccine uses a recombinant protein created by GSK scientists that fuses part of the P.falciparum circumsporozoite protein (CSP) with hepatitis B surface antigen. 7/3/08 13 A Global Network of Partners in 34 Countries: Academia, Industry and Clinical research entres: University of California, San Francisco University of Washington Liverpool School of Tropical Medicine University of Liverpool Oxford University GlaxoSmithKline LSHTM STI Immtech International F. Hoffmann-La Roche GlaxoSmithKline Novartis Pharma University of Iowa WHO/(TDR) Yale University Sigma-Tau Industrie Farmaceutiche Riunite Albert Einstein College of Medicine Ranbaxy Laboratories Limited GlaxoSmithKline WRAIR Tres Cantos Texas A&M National Institutes of Health (NIH) Korea Shin Poong Pharm. Inc. Holley Pharma University of North Carolina Chapel Hill University of Mississippi University of Nebraska Medical Center BIOTEC Mahidol University University of Buea, Cameroon = Pharmaceutical partner = University/institute = National research institute = Clinical trial site ( = under review) 7/3/08 = International agency Everyday, more than 800 scientists, doctors and clinicians are working on developing new antimalarials Monash University 14 ANTI CANCER VACCINE: • Cell Genesys' GVAX® lung cancer vaccine is a patient-specific vaccine designed to induce a systemic immune response against the patient's lung cancer. • The vaccine is made by directly modifying the patient's tumor cells. After surgical removal of a patient's tumor, the GVAX® cancer vaccine is prepared by culturing and genetically modifying the patient's tumor cells to secrete GM-CSF.The cells are then irradiated for safety prior to vaccinating the patient. 7/3/08 15 • Cell Genesys will conduct two Phase 2 clinical trials evaluating GVAX® lung cancer vaccine. The first of these Phase 2 trials is sponsored by Cell Genesys and is enrolling patients with all subtypes of non small-cell lung cancer. Patients are being randomized to receive GVAX® lung cancer vaccine with or without low-dose cyclophosphamide. • The second Phase 2 trial, which is sponsored and partially funded by the Southwest Oncology Group (SWOG), a cooperative clinical trials group of the National Cancer Institute (NCI), is focused on patients with the bronchoalveolar carcinoma (BAC) subtype of non small-cell lung cancer. 7/3/08 16 ANTI TB VACCINE: • Austrian vaccine developer Intercell has launched Phase I clinical trials of a new preventive tuberculosis vaccine. The company is working with the Statens Serum Institute and the Aeras Global TB Vaccine Foundation to develop the vaccine. • The vaccine, called HyVac4-IC31, is being tested among individuals who have been vaccinated with the BCG vaccine, Trials are taking place at the Karolinska Instituted in Stockholm, Sweden. 7/3/08 17 • The vaccine's adjuvant, IC31, has "proven to be safe and induce a strong and sustained immune response. • The vaccine also has "induced more significant protection in a BCG prime-boost regimen than any other vaccine we have tested in the long-term guinea pig challenge model. 7/3/08 18 VACCINE FOR ASTHMA: • Wyeth has successfully completed Phase I trials for asthma vaccine. • Etanercept is being evaluated for moderate to severe asthma. • The recruitment is complete for Phase II trials. • The primary objective of the study is to assess the efficacy and safety of Etanercept 25 mg given twice weekly in subjects with moderate to severe persistent asthma. • 120 subjects between age group of 18 to 70 years, of both genders are included in the trial. • Change in FEV1% is predicted from baseline to week 12. 7/3/08 19 ORPHAN DISEASE VACCINES: • Intercell company’s Japanese Encephalitis vaccine, currently in advanced Phase III trials, has been granted orphan drug status by the European Commission. • This Japanese Encephalitis vaccine is a purified, inactivated vaccine for active immunization of adults against the Japanese Encephalitis virus and has successfully concluded Phase II clinical trials. • In a Phase II head to head comparison between JE VAX, Intercell’s vaccine was shown to be: → Less Reactogenic → More potent → More convenient → More persistent 7/3/08 20 PIPELINE VACCINES: Adenovirus Campylobacter jejuni Cytomegalovirus Encephalitis, eastern equine Encephalitis, Japanese Encephalitis, tick-borne Encephalitis, Venezuelan equine Encephalitis, western equine Enterohemorrhagic Escherichia coli E coli urinary tract infections Epstein-Barr virus Extended serotype conjugate pneumococcal vaccines Groups A and B streptococci Haemophilus ducreyi (chancroid) Hepatitis C Herpes simplex virus types 1 and 2 HIV Human papillomavirus Influenza Malaria Meningococci (conjugates and combination vaccines) Mycobacteria (Mycobacterium tuberculosis, Mycobacterium leprae) Neisseria gonorrhoeae Non-typeable Haemophilus influenzae and Moraxella species Parainfluenza Pertussis (adult) Respiratory syncytial virus Rotavirus 7/3/08 Salmonella Shigella 21 GUIDELINES FOR VACCINE STUDIES: • Subject should be aware that active or live attenuated micro-organism can possibly cause particular infection. • Subjects in control group with ineffective vaccine could contract the disease. • Risks associated with recombinant DNA technology vaccines are not completely known. Guidelines issued by Department of Biotechnology should be followed. • Investigator selected for their studies should have experience, infrastructure and lab for evaluation of seroconversion. • Principal investigator should be provided with the QC data of the experimental batch of vaccine produced for the trial. • PMS should be performed following seroconversion studies to detect side effects in a huge population. 22 PROTOCOL REQUIREMENTS: • Selection of subject • Frequency of administration • Testing method to detect antibody titer should be validated • Storage condition and investigational product handling requirements 7/3/08 23 CHALLENGES IN VACCINE STUDIES: • Recruitment of subjects • Informed consent • Cost • Preservation • Potency • Immunocompromised patients • Elicit an immune response: that does not actually protect against the disease. 7/3/08 24 SUMMARY: • New vaccines against emerging diseases are usually based on the established vaccines. • Despite the tremendous impact that vaccines have had on global health, there is a still considerable work to be done scientifically and politically. • The correlates of protection against pathogen such as HIV1 and TB remain among the most important problem to solve. • Furthermore, since results in animal models and results in man often differ considerably, it is important to test more vaccine candidates in clinical trials. 7/3/08 25 REFERENCES: • • • • • • • www.iavi.org www.hvtn.org www.malaria-vaccines.org.uk www.cellgenesys.com www.icmr.nic.in www.who.int www.wyeth.com 26 7/3/08 7/3/08 27