Since chemoprophylaxis and vector control measures have been unsuccessful in controlling human malaria, the need for a vaccine, especially for Plasmodium falciparum, is apparent. Recently, protective antigens with potential use in a vaccine to the sporozoite and gametocyte stages of malaria have been identified using hybridoma technology. However, protective antigens present in the erythrocytic stage still need to be identified. The most likely location of such antigens are on merozoites and the surface of infected erythrocytes. Numerous researchers are analyzing merozoite-associated antigens using monoclonal antibodies, but, to my knowledge, no one currently is applying this technology to identify and isolate antigens expressed on the surface of P. falciparum-infected cells. Dense, cup-shaped protrusions appear on the surface of infected cells called knobs, that are involved in sequestering infected cells in deep vascular tissue. Such sequestration in brain venules may lead to cerebral malaria. Very little is known about the antigenicity of knobs, or if infected cells possess other surface antigens. It is probably that the induction of antibodies to knob antigens by vaccination would prevent sequestration, thus helping prevent cerebral malaria and subjecting late-stage parasites to immunologic destruction in the spleen. I propose in this application to produce monoclonal antibodies to antigens on P. falciparum-infected erythrocytes, especially those associated with knobs, and then use them to: identify antigens involved in endothelial attachment, evaluate the effect of specific antibodies on enhancing phagocytosis, and determine if monoclonal antibodies will mediate lysis of infected erythrocytes by complement or direct granulocyte contact.

Information gained from this study should help identify, and assess, the potential of erythrocyte surface antigens for inclusion in a vaccine against P. falciparum.

R01AI020917

1984-12-01

1988-11-30