Project Title

Harnessing parasite diversity and naturally acquired protective immunity against Plasmodium falciparum malaria for the development of highly effective vaccines (SMART)

EDCTP Project Call

Senior Fellowship (SF)

Project Objectives

To support the development and maintenance of highly effective vaccines against Plasmodium falciparum malaria in the long term by: 1. Monitoring population-level antigen specific parasite diversity of a comprehensive panel of vaccine candidates 2. Investing in the human capacity for basic science research in sub-Saharan Africa

Study Design

The project takes advantage of retrospectively collected samples that are available from multi-centre cohort studies (MCS). The MCS all employed a prospective longitudinal cohort study design, in which children were sampled at the start of the study and subsequently monitored for clinical episodes of malaria (end-point) through home or clinic visits over the subsequent 6 months to 1 year post-sampling. Parasites are genotyped from samples collected at the start of the study, and at all subsequent points during the observation period. The MCS included in this project were purposively selected to represent the broad range of malaria transmission intensities present in Sub-Saharan Africa.

Project Summary

Background: Plasmodium falciparum malaria remains a major public health concern in Africa where it has an unacceptably high death toll; over 400,000 children are estimated to have died of malaria in 2014. Although current control efforts have had modest success, they face the continual challenge of drug resistance. The consensus view is that malaria elimination in Africa will require the addition of highly effective malaria vaccines. Building the capacity to drive the science of malaria vaccine development within Africa is essential for long-term success and sustainability. Concept: This proposal aims to build on ongoing funded studies aimed at “Defining the merozoite targets of protective immunity against P. falciparum malaria through multi-centre cohort studies” (Osier, MRC/DFID African Research Leader Award) with concurrent analyses of local parasite diversity in multiple African populations. It will provide a rich and high quality data resource for the malaria research and vaccine development community whilst simultaneously providing a platform for training African PhD students. By using retrospectively collected samples, I will also maximize the impact of previous and ongoing funding investments at multiple locations in Africa. Rationale: The limited efficacy of the most advanced malaria vaccine in Phase III clinical trials has been linked to the induction of allele-specific immunity. The mismatch between “vaccine alleles” and those in the parasites causing clinical infections was also thought to account for the limited efficacy of MSP2-, MSP1- and AMA1-based malaria vaccines in previous Phase IIb clinical trials. This proposal aims to genotype parasite isolates at genetic loci that encode proteins that are strongly correlated with protection from clinical episodes of malaria in multiple African sites. We will focus on newly-identified or insufficiently-studied antigens that could contribute to the development of a multi-component malaria vaccine. The ability to monitor vaccine antigen diversity in local populations is key for the long-term sustainability of vaccination against malaria. Training: This proposal will support the training of 3 high caliber PhD students from West Africa. Together with additional funding leveraged by the lead applicant, the SMART network will also provide a platform for the shortterm training of 2 African Post-docs, 5 Masters students and up to 15 post graduate-diploma students over the duration of the EDCTP Senior Fellowship.

Host Organisation

Current Organisation

Kenya Medical Research Institute (KEMRI); Centre for Infectious Diseases, Parasitology, Heidelberg University Medical Faculty

Current Job Title

Professor of Immunology | Group Leader, Malaria Vaccine Development

Biography