Post on 16-Jan-2016
Malaria vaccine development:Recent 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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A world free from malaria
Established in 1999 as a program of PATH.Current donors: Bill & Melinda Gates Foundation,
USAID, ExxonMobil Foundation, private individuals
PATH Malaria Vaccine InitiativeMission and vision
To accelerate the development of malaria
vaccines and ensuretheir availability and accessibility in the developing world
MVI: a global programof PATH
PATH: a catalyst for global health
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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 M&E 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
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 candidate’s success?
Commercial:– Limited market in developed countries– Endemic countries mostly poor– High-risk, high-level investment
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
KCCR, Kumasi
Gabon
IRSS - Centre MurazBurkina Faso
KHRC, Kintampo
Ghana
HAS, LambarénéKenya
Tanzania
IHDRC, Bagamoyo, Tanzania
KEMRI/WRAIR – Kombewa
JMP, Korogwe, Tanzania
KEMRI/CDC – Siaya
KEMRI/Kilifi
UNC, LilongweMalawi
CISM, ManhiçaMozambique
RTS,S project is MVI’s largest collaboration
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.
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Preclinical Feasibility* Translational ProjectCandidateVaccines
Antigens Delivery Preclinical Phase 1 Phase 2a Phase 2b Phase 3
SBRI(antigen
selection)
Aeras(rBCG)
Crucell
(Ad26/35-CSP)
Sanaria
(whole irradiated sporozoite)
GSK
(RTS,S/AS01)
WEHI(AMA1)
GenVec
(Ad28)ICGEB(PvRII)
LaTrobe/QIMR(MSP2)
LaTrobe/WRAIR(AMA1)
VGX/U Penn(pDNA/EP)
NIH/QIMR
(AMA1)
WEHI/NIH(EBA/Rh
Lipoxen/NIH(Imu/Xen)
Juvaris/NIH(JVRS-100)
USMMVP/NIH/GenVec
(Ad5/Protein+Adj)
NIH(conjugates)
Pre-erythrocytic
Blood-stage
Transmission-blocking
MVI Portfolio
*Selected projects
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MVI collaborators include…
SANARIAMALARIA ERADICATION THROUGH VACCINATION
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
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
Pre-erythrocytic Stage
Prevent infection
Blood-stage Reduce clinical disease
Transmission-blocking
Prevent the spread of parasites by mosquitoes
Different types of vaccine target different stages of the lifecycle
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Transmission-blocking vaccines target the parasite in the mosquito—and 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 (1:2) from baboons immunized with CH-rPfs48/45 in Montanide ISA-51
# 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
Nov 10 Dec 10 Jan 10 Feb 5 Feb 21 Mar 6 May 5
Primary 1st boost 2nd boost
Time points of various bleeds from animals
A
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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
Final thoughts…
• Malaria eradication will not happen without vaccines
• Funding for R&D —and introduction — is needed
• CollaborationCoordinationCommitment
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Tomorrow…
Thank You
www.path.org
www.malariavaccine.org