ANTIBODIES INHIBIT THE PROTEASE-MEDIATED PROCESSING OF A MALARIA MEROZOITE SURFACE PROTEIN

When merozoites of the malaria parasite Plasmodium falciparum are rele ased from infected erythrocytes and invade new red cells, a component of a protein complex derived from the merozoite surface protein 1 (MSP -1) precursor undergoes a single proteolytic cleavage known as seconda ry processing. This releases the complex from the parasite surface, ex cept for a small membrane-bound fragment consisting of two epidermal g rowth factor (EGF)-like domains, which is the only part of MSP-1 to be carried into invaded erythrocytes. We report that, of a group of mono clonal antibodies specific for epitopes within the EGF-like domains, s ome interfere with secondary processing whereas others do not. Those t hat most effectively inhibit processing have previously been shown to prevent invasion. Other antibodies, some of which can block this inhib ition, not only do not prevent invasion but are carried into the host cell bound to the merozoite surface. These observations unequivocally demonstrate that the binding of antibody to the COOH-terminal region o f MSP-1 on the merozoite surface may not be sufficient to prevent eryt hrocyte invasion, and show that the interaction of different antibodie s with adjacent epitopes within the EGF-like domains of MSP-1 can have distinct biochemical effects on the molecule. Inhibition of MSP-1 pro cessing on merozoites may be a mechanism by which protective antibodie s interrupt the asexual cycle of the malaria parasite.