The overall, long term objective of the proposed research is to add to our knowledge about new Plasmodium falciparum merozoite antigens that could be included as components of a multivalent blood stage based vaccine formulation. A number of vaccine candidate antigens based on a few characterized falciparum malaria merozoite proteins are currently being advanced or targeted for advancement through primate and phase l and Il clinical trials for vaccine evaluation and development. These include the antigens MSP-1, MSP-2, SERA, RESA, RAP-1, RAP-2, and AMA-1. Whether these first generation candidates will prove to have the desired efficacy in humans, alone or in various combinations, is not known at this time. The malaria merozoite and the molecular events of red blood cell invasion are complex and as yet uncharacterized proteins potentially useful as immunogens likely exist. One prudent course for fundamental malaria vaccine studies, in light of the uncertainties at this time about the current vaccine candidates, would be to continue to advance our knowledge about the biology and novel molecular components of the malarial merozoite. Thus, the specific aims of the research proposed here is to characterize and evaluate in some depth two new merozoite proteins of P. falciparum in regards to biological function and potential for induction of protective immune responses. These two protein antigens include (1) an unreported P. falciparum erythrocyte binding receptor protein, previously hypothesized to exist but was not identified, and (2) a novel moderately asparagine- rich apically oriented merozoite protein. The gene(s) for the erythrocyte binding protein doublet will be cloned and the functional binding domain(s) will be identified. The gene for the merozoite apically oriented protein will be completed and potential sequence polymorphisms will be thoroughly evaluated. Antisera to recombinantly expressed antigens corresponding to these two merozoite proteins will be evaluated for the ability to recognize the native proteins and in vitro block merozoite invasion. The study of these two parasite proteins will proteins will lead to the advancement of our knowledge about merozoite biology and the potential inclusion of new additional blood stage proteins as candidate antigens in a vaccine against malignant tertian malaria.
