malaria vaccine development: recent progress, future challenges christian loucq, md director, path...

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)

2

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