Group a Pfemp1 functional domains bind icam1 and induce cross-reactive and adhesion inhibitory antibodies during malaria infections

The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) plays an important role in antigenic variation and pathogenesis of malaria. PfEMP1 proteins encoded by group A var genes appear to be involved in the pathogenesis of severe disease and have been suggested as attractive candidates for a vaccine against life-threatening P. falciparum malaria.

In this study, we identified group A pfd1235w-like genes in Ghanaian isolates and found these to encode a three-domain cassette structure 64-80% identical to the equivalent region of P. falciparum clone 3D7 PFD1235w. Parasites expressing PFD1235w-like proteins on the surface of infected erythrocytes were found to mediate binding to ICAM1, a phenotype linked to cerebral malaria.

ICAM1 binding was mediated by a particular sub-domain which induces cross-reactive and ICAM1 adhesioninhibitory antibodies during P. falciparum infections. These results have implications for our understanding of how PfEMP1 interacts with host receptors and for the development of therapeutic interventions targeting ICAM1 binding malaria parasites.