High-throughput testing of antibody-dependent binding inhibition of placental malaria parasites

Abstract

The particular virulence of Plasmodium falciparum manifests in diverse severe malaria syndromes as cerebral malaria, severe anemia and placental malaria. The cause of both the severity and the diversity of infection outcome, is the ability of the infected erythrocyte (IE) to bind a range of different human receptors through Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of the infected cell. As the vargenes encoding the large PfEMP1 antigens are extensively polymorphic, vaccine development strategies are focused on targeting the functional binding epitopes. This involves identification of recombinant fragments of PfEMP1s that induce antibodies, which hinder the adhesion of the IE to a given receptor or tissue. Different assays to measure the blocking of adhesion have been described in the literature, each with different advantages. This chapter describes a high-throughput assay used in the preclinical and clinical development of a VAR2CSA based vaccine against placental malaria.