Plasmodium Falciparum Malaria Invasion Ligand as a Vacci

The erythrocytic stage of Plasmodium falciparum kills an estimated 2 million children annually.The parasite invades erythrocytes (RBCs) by attaching to surface receptors, one of which involves sialicacids. The 175 kD P. falciparum protein, erythrocyte binding antigen (BBA-175), binds to RBCs in asialic acid dependent, receptor-specific fashion. The ability of EBA-l75 to bind to RBCs correlates withthe ability of these RBCs to be invaded by parasites. The actual sialic acid binding domain of EBA-175(region ll) has recently been identified. Our specific aim is to determine if antibodies against region ll ofEBA-175 will block merozoite invasion of RBCs indicating that region H should be developed as a malariavaccine. To accomplish this goal, a plasmid construct with region H of EBA-175 will be expressed by2 methods in mammalian and prokaryotic cells, and the expressed proteins assessed for their capacityto produce functionally active antibodies. The short term goals of this proposal are l) to determine ifregion ll can induce functional antibodies, and 2) to determine which expression method induces themost functionally active antibodies. The long term goal is to assess the safety, immunogenicity, andprotective efficacy of the best immunogen first in Aotus monkeys, and then in humans.