Evidence is emerging that immunity against malaria is to a large degree due to humoral responses against variable antigens located on the surface of infected erythrocytes. Plasmodium falciparum, once in the red blood cell, substantially modifies the cell and, besides establishing the whole machinery for protein synthesis and transport, places a molecule into the erythrocyte membrane. This protein (PfEMP1) confers binding to endothelial cells and is considered to be the major virulence factor in malaria. However, this molecule displays significant antigenic variation, i.e. changes its antigenic property to escape elicited immune responses. Because of this, development of a vaccine based on this molecule has been considered impossible.

However, several pieces of evidence suggest otherwise. First, during pregnancy, parasites infecting the placenta commonly express one particular PfEMP1 molecule (varCSA) and thus a vaccine against pregnancy associated malaria is being developed based on this one form of PfEMP1. Secondly, a large number of PfEMP1 molecules bind to an epithelial cell protein, CD36, and recently a structural conservation of the head structure of PfEMP1 has been shown. Therefore, it seems feasible to develop a vaccine based on these structural features to block binding to CD36. Thirdly, additional evidence is emerging that parasites causing severe disease and adhering to tissues in essential organs (brain, lung, kidneys, etc.) display only a limited number of PfEMP1 molecules, and the identification of these molecules could lead to a disease blocking vaccine. Fourthly and finally, it is now possible to genetically modify parasites in such way that no PfEMP1 can be produced or no PfEMP1 will be exposed on the surface. As an experimental approach it is feasible to use these modified strains as genetically attenuated parasites (GAPs) to study immune responses elicited.
At the STI research department ‘Medical Parasitology and Infection Biology’ research is conducted into the last two approaches, identification of virulence associated PfEMP1 molecules and production of PfEMP1 negative mutants to be used as experimental GAPs.

Prof. Hans-Peter Beck

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