Malaria vaccine development: Recent progress, future challenges

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Malaria vaccine developmentRecent progress,
future challenges
Christian Loucq, MDDirector, PATH Malaria
Vaccine Initiative All Party Parliamentary Group
on Malariaand Neglected Tropical
DiseasesOctober 26, 2009
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PATH Malaria Vaccine InitiativeMission and vision
To accelerate the development of malaria vaccines
and ensuretheir 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,USAID,
ExxonMobil Foundation, private individuals
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PATH a catalyst for global health
MVI a global programof PATH
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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 ME in Zambia
• Partner in the development of the RBM MERG
  Malaria Indicator Survey (MIS)
• Document and disseminate success stories

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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

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Why a malaria vaccine?

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

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Why a malaria vaccine?
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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

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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 candidates success?
• Commercial
• Limited market in developed countries
• Endemic countries mostly poor
• High-risk, high-level investment

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Where are we today?

• Worlds 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

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RTS,S project is MVIs largest collaboration
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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

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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.

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MVI Portfolio
Selected projects
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MVI collaborators include
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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

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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?

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Goal Malaria eradication
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What comes next?

• Focus on questions to be answered

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Different types of vaccine target different
stages of the lifecycle

• Pre-erythrocytic vaccines
• Blood-stage vaccines
• Transmission-blocking vaccines

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Different types of vaccine target different
stages of the lifecycle
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Transmission-blocking vaccines target the
parasite in the mosquitoand mosquito itself
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Transmission-blocking vaccines

• Goal Interrupt lifecycle to reduce transmission
  
• Strategies
• 1. Block production of gametocytes
• (highly effective PE vaccine)
• 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)

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1
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MFA with sera (12) from baboons immunized with
CH-rPfs48/45 in Montanide ISA-51
Doses Blocking (MFA) Primary 93 3
(8894) Boost 1 97 1 (9598) Boost 2
(15d) 97 1 (9599) Boost 2 (30 d) 97 1
(9698) Boost 2 (3 mo) 97 1 (9599)
Chowdhury, DR. et al. PLoS One July 2009.
4(7)110
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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

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Vaccines Critical component of coordinated
eradication effort

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

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Final thoughts

• Malaria eradication will not happen without
  vaccines
• Funding for RD and introduction is needed
• CollaborationCoordinationCommitment

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Tomorrow
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Thank You

• www.path.org
• www.malariavaccine.org