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London School of Hygiene & Tropical Medicine Malaria Centre

Malaria research in parasite biology

Alternative molecular mechanisms for erythrocyte invasion by Plasmodium falciparum in Ghana.

LSHTM investigators:
David Conway
External collaborators:
Gordon Awandare (University of Ghana, Ghana); Seth Ogusu-Agyei (Kintampo Health Research Centre, Ghana); Abraham Oduro (Navrongo Health Research Centre, Ghana).
Funding body:
Royal Society-Leverhulme Africa Award.

Development of a blood stage vaccine is hampered by inadequate understanding of the mechanisms by which the parasite invades erythrocytes and evades immune responses. The invasive merozoite stage of Plasmodium falciparum has an extensive array of ligands, each interacting with one or more receptors on the erythrocyte surface.

The identity of sialic acid (SA)-independent erythrocyte receptors were unknown until Dr Gordon Awandare and colleagues identified complement receptor 1 (CR1) as the major SA-independent invasion receptor, and subsequent studies implicated the Rh4 protein of Plasmodium falciparum as the ligand for CR1. We propose that one mechanism by which Plasmodium falciparum merozoites evade immune responses is by altering ligand gene expression that allows a switch in invasion phenotypes as antibodies targeting the existing mechanisms are developed. The current study involves analysis of clinical isolates from different endemic sites to addresses the following aims:

  • To determine the erythrocyte invasion phenotypes of Ghanaian Plasmodium falciparum isolates and their relative dependence on different receptors including CR1.
  • To determine the impact of selection by host antibodies on gene expression profiles of Plasmodium falciparum ligands involved in SA-independent invasion.
  • To identify polymorphisms in parasite genes associated with escape from anti-SA ligand antibodies.