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Christian Loucq MVI Oct 26 09

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Christian Loucq MVI Oct 26 09 Powered By Docstoc
					Malaria vaccine development:
Recent progress, future challenges



Christian Loucq, MD
Director, PATH Malaria Vaccine Initiative

All Party Parliamentary Group on Malaria
and Neglected Tropical Diseases
October 26, 2009
PATH Malaria Vaccine Initiative
Mission and vision


                                      To accelerate the
                                   development of malaria
                                    vaccines and ensure
                                    their availability and
                                     accessibility in the
                                      developing world


                                           A world free
                                           from malaria

             Established in 1999 as a program of PATH.
          Current donors: Bill & Melinda Gates Foundation,   2
         USAID, ExxonMobil Foundation, private individuals
PATH: a catalyst for
global health

MVI: a global program
of PATH
Role of MACEPA

• Many groups/organizations involved in the purchasing
  and distribution of bednets, few are measuring impact
  of the interventions
• One of the important roles of MACEPA— supported
  the coordination of malaria M&E in Zambia
• Partner in the development of the RBM MERG Malaria
  Indicator Survey (MIS)
• Document and disseminate success stories




                                                     4
PATH background

• International nonprofit to help provide appropriate
  health technologies and vital strategies to improve
  global health and well-being
• Particular focus on:
   –   HIV, TB, and malaria (MACEPA and MVI)
   –   Health technologies designed for low-resource settings
   –   Safer childbirth and healthy children
   –   Health equity for women
   –   Basic protection of vaccines




                                                                5
Why a malaria vaccine?

                    • Malaria
                         – 900,000 deaths
                         – US$ 12 billion
                         – 40 percent of public
                           health spending
                    • Control
                    • Elimination /
                      Eradication

                                             6
Why a malaria vaccine?
Malaria 101

• A parasitic infection transmitted to
  humans through the bite of infected
  female Anopheles mosquitoes

• Five Plasmodium sp. infect humans;
  falciparum and vivax cause the vast
  majority of clinical cases

• Almost all serious disease/deaths are
  caused by P. falciparum malaria in
  children under 5 years of age
                                          8
Challenges to developing malaria vaccines


• Scientific:
   –   No vaccine is in human use against a parasite
   –   Malaria parasite has ~6,000 genes, many more than a virus
   –   How best to provoke immune response?
   –   How to predict a vaccine candidate’s success?


Commercial:
   – Limited market in developed countries
   – Endemic countries mostly poor
   – High-risk, high-level investment


                                                               9
Where are we today?

• World’s most clinically advanced vaccine
  candidate is RTS,S

• Collaboration with GSK Bio (Belgium),
  11 study centers (in seven African
  countries), and Northern institutions

• Phase 3 trial now up and running in all seven
  countries, 10 of 11 sites
     RTS,S project is MVI’s largest collaboration


IRSS - Centre Muraz
Burkina Faso




                      KHRC, Kintampo
                      KCCR, Kumasi                            KEMRI/WRAIR – Kombewa
                      Ghana                                   KEMRI/CDC – Siaya
                                                              KEMRI/Kilifi
                                                             Kenya
                                       HAS, Lambaréné
                                       Gabon                  JMP, Korogwe, Tanzania
                                                              IHDRC, Bagamoyo, Tanzania
                                                             Tanzania




                                                         UNC, Lilongwe
                                                         Malawi




                                                        CISM, Manhiça
                                                        Mozambique
Where are we today?

• A second vaccine approach approved for
  first-in-human trial in the United States

• Sanaria Inc. seeks to replicate original
  experiment with irradiated mosquitoes
How MVI works

• MVI partners to achieve its mission; success depends
  on the strength of its collaborations

• MVI is a non-profit vaccine investor. Partners include
  academia, government agencies, biotechs,
  pharmaceutical companies

• MVI identifies potentially promising malaria vaccine
  candidates and approaches, then…

• MVI systematically move candidates and approaches
  through the development process.
     MVI Portfolio
                                                                                                  Candidate
Preclinical Feasibility*                           Translational Project
                                                                                                  Vaccines
  Antigens            Delivery       Preclinical     Phase 1          Phase 2a         Phase 2b    Phase 3

     SBRI                              Crucell                 Sanaria                                GSK
                        Aeras
   (antigen                           (Ad26/35-     (whole irradiated sporozoite)                 (RTS,S/AS01)
                       (rBCG)
  selection)                            CSP)

                       GenVec                      LaTrobe/QIMR
    WEHI                               ICGEB
                                                      (MSP2)
   (AMA1)              (Ad28)          (PvRII)

LaTrobe/WRAIR        VGX/U Penn                     NIH/QIMR
    (AMA1)            (pDNA/EP)                      (AMA1)

  WEHI/NIH           Lipoxen/NIH
  (EBA/Rh             (Imu/Xen)

                     Juvaris/NIH
                     (JVRS-100)

                 USMMVP/NIH/
                   GenVec
                 (Ad5/Protein+Adj)
                                                                    Pre-erythrocytic

                         NIH                                        Blood-stage
                     (conjugates)
                                                                    Transmission-
                                                                    blocking                             14
*Selected projects
MVI collaborators include…



                             SANARIA
                             MALARIA ERADICATION THROUGH VACCINATION




                                                                       15
Goals in sight?

• Vaccine goal for 2015 in sight
  – 50% efficacy against severe disease
  – Lasts more than one year
  – Another tool to achieve malaria control
• Next-generation vaccine could be
  in the pipeline now
  – Higher efficacy, lasts longer than 4 years
  – Transmission blocking?
  – Key to malaria elimination, eradication
Malaria vaccine community goal

• By 2025, to develop and license a malaria
  vaccine that has a protective efficacy of more
  than 80% against clinical disease and lasts
  longer than four years

     BUT,

• Could we do more?


                                               17
Goal: Malaria eradication




                            18
What comes next?




• Focus on
  questions
  to be
  answered
Different types of vaccine target
different stages of the lifecycle

• Pre-erythrocytic vaccines

• Blood-stage vaccines

• Transmission-blocking
  vaccines



                                    20
  Different types of vaccine target
  different stages of the lifecycle

Pre-erythrocytic   Prevent
Stage              infection

Blood-stage        Reduce
                   clinical
                   disease
Transmission-      Prevent the
blocking           spread of
                   parasites by
                   mosquitoes
Transmission-blocking vaccines target the
parasite in the mosquito—and mosquito itself




                                          22
Transmission-blocking vaccines

• Goal: Interrupt lifecycle to reduce
  transmission

• Strategies:
   1. Block production of gametocytes 2
      (highly effective PE vaccine)                  1
   2. Block oocyst formation in mosquito
      (prevent transmission of the disease)

• TBVs target transmission:
   – No direct, immediate benefit to vaccinee
   – Infections reduced due to reduced
     transmission (herd effect)
                                                23
MFA with sera (1:2) from baboons immunized
with CH-rPfs48/45 in Montanide ISA-51
    A
        Primary 1st boost          2nd boost

        Nov 10   Dec 10   Jan 10   Feb 5   Feb 21     Mar 6   May 5


         Time points of various bleeds from animals



         # Doses                                    % Blocking (MFA)
         Primary                                       93 + 3 (88–94)
         Boost 1                                       97 + 1 (95–98)
         Boost 2 (15d)                                 97 + 1 (95–99)
         Boost 2 (30 d)                                97 + 1 (96–98)
         Boost 2 (3 mo)                                97 + 1 (95–99)


Chowdhury, DR. et al. PLoS One July 2009. 4(7):1–10                     24
MFA to evaluate transmission blocking
antibodies




 • Cultured serum + gametocytes fed to starved mosquitoes through
   membrane
 • Count oocysts in midgut 1 week later.
 • Result: % oocyst reduction                                   25
Vaccines: Critical component of
coordinated eradication effort

• Vector control
   – Insecticide treated bednets
   – Indoor residual spraying
   – Integrated vector management
• Drug therapy
• Vaccines




                                    26
 Final thoughts…

• Malaria eradication
  will not happen
  without vaccines

• Funding for R&D —
  and introduction — is
  needed

• Collaboration
  Coordination
  Commitment
Tomorrow…




            28
  Thank You
    www.path.org
www.malariavaccine.org

				
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