Last Updated: 19/06/2024
Super-epitopes in severe malaria
Objectives
The aim of this project is to identify specific structures in Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) that induce broad and potent antibodies inhibiting sequestration in severe malaria. In the approach to achieve this ambitious goal, the researchers will develop new methods for the identification of surface exposed epitopes, cross-reactivities between epitopes and receptor-binding structures in PfEMP1.
Plasmodium falciparum undergoes antigenic variation to establish persistent blood stage infections. The major variant antigen, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), is expressed at the erythrocyte surface where it acts as a virulence adhesion molecule bringing about severe malaria through accumulation of infected and uninfected erythrocytes in the micro-vasculature. The researchers hypothesize that subgroups of cross-reactive PfEMP1 sequences are recognized by the immune-system and that certain antibodies are key in the protection against severe malaria. The objective of this project will be accomplished in five parallel discovery programs and in one for validation including isolation of I) antibodies to PfEMP1, II) cross-reactive IgG on random- and specific peptide libraries, III) human memory B cells/ antibodies, IV) fresh isolates from Uganda and V) creation of a super cross-reactive epitope. Candidate structures will be validated using state-of-the-art methods to investigate the specificity, quality and quantity of immunity to PfEMP1. The project is likely to reveal the Achilles heal of the parasites immune evasion strategy and will be useful for the design of a vaccine.
Jan 2012 — Dec 2016
$1.56M
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