This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term objective of this research is to provide basic fundamental molecular biological and immunobiological information that will aid in the development of a blood stage merozoite vaccine against Plasmodium vivax, one of the two most prevalent species of human malaria. This research is also relevant for increasing the understanding of the biology of P. falciparum merozoites, the other major species of human malaria. The related non-human primate malarias P. cynomolgi, P. coatneyi and P. knowlesi, which infected rhesus monkeys, are excellent models for these investigations. This project entails the characterization of several Plasmodium merozoite proteins and the genes encoding them, with emphasis on molecules that 1) have an apparent direct or indirect function in the receptor mediated processes of merozoite invasion of erythrocytes, and 2) are likely to have a role in affecting the immunobiological relationship between P. vivax and humans by stimulating anti-P. vivax immune responses. Three of these form a family that may also have a paradoxical role of promoting chronicity. The research is aimed at investigating aspects of the genetics and diversity of the family members and how this may affect the immune response mechanisms induced by these proteins. The coordinated use of in-vitro merozoite invasion and attachment assays, immunoelectron microscopy, gene knockout technologies, defined antibody and recombinant DNA reagents, and the use of the simian malaria models, aid in the precise determination and clarification of the location(s), function, structure and possible interactive relationships of the merozoite proteins under investigation. Understanding these properties is important for the rational development of potential malaria vaccine candidates. This past year special emphasis has been on interspecies comparative analyses, the evaluation of putative erythrocyte adhesion domains, development and expression of vaccine constructs, and ongoing studies evaluating the naturally acquire immune responses produced against these proteins.
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