Current Organisation

National Institute for Medical Research (NIMR)

Current Job Title

Professor

Biography

Publications

Project Title

Malaria Research Capacity building for Field Trials in Tanzania (MaReCa)

EDCTP Project Call

Senior Fellowship (SF)

Host Organisation

Project Objectives

1. To document burden of malaria in the study area over years 2. To develop and characterize efficacious malaria vaccine for children and pregnant women. 3. To build malaria research capacity at Masters and PhD levels. 4. To establish and maintain mentorship programme. 5. To sustain clinical research and clinical trials in Korogwe Research Station.

Study Design

Longitudinal cohort study

Project Summary

The most deadly form of malaria is caused by Plasmodium falciparum, that expresses antigens on the surface of the infected erythrocyte that enable the parasite to sequester to the vascular endothelium. The binding is mediated by a family of antigens called Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) encoded by about 60 var genes in each genome. Protective antibodies block the binding between the infected red blood cells and receptors on vascular endothelium. Due to the extensive variation within the PfEMP1 family a large repertoire of antibodies is needed before the individual is completely protected. Protection against severe forms of malaria is acquired after a few infections such as pregnancy-associated malaria. Here disease is caused by parasites expressing the variant of PfEMP1 called VAR2CSA, and anti-VAR2CSA antibodies mediate immunity against the syndrome. Recently we identified Endothelial Protein C Receptor (EPCR) as the most pathogenic PfEMP1 in severe malaria in children, and we need to characterize it by using well defined malaria patients. Interestingly vaccines based on PfEMP1 are attractive because they mimic natural occurring protective immune responses and could avert syndromes responsible for the vast proportion of malaria deaths. The theoretical background for our approach is that antibodies that prevent the interaction between PfEMP1 and its receptors are the main targets for acquired immunity, and that such antibodies can be induced by vaccination. To pursue the goal of making malaria vaccines, we will use bioinformatics, molecular biology, gene technologies, protein chemistry, structural chemistry, immunology, parasitology, vaccinology and clinical sciences. The vaccines that we are aiming to develop will be subject to administration to young children and women. The mosquirix (RTS,S/AS01) malaria vaccine protective efficacy is moderate and requires four doses. A more efficacious vaccine would be ideal and that is why we believe a PfEMP1 based malaria vaccine would meet such demands. The venture towards placental malaria vaccine and more efficacious malaria vaccine for children requires the availability of qualified scientists to conduct field trials in malaria endemic communities and apply molecular, immunology, parasitology and genomics to evaluate malaria vaccines at different stages of clinical development. We believe that through a Senior Fellowship whereby a field team will be established in Korogwe and sustained through the fellowship as well as capacity development at Masters and PhD level for junior research scientist, the site will be readily prepared to test vaccine for placental malaria and a more potent malaria vaccine for children.

Results & Outcomes