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MOLECULAR ANALYSIS OF PLASMODIUM VIVAX SURFACE ANTIGENS

$54,827P51FY2010RRNIH

Emory University, Atlanta GA

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Linked publications & trials

Abstract

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 fundamental molecular biological and immunobiological information tosupport the development of a blood-stage 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, 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. 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. This year, our report on the identification of the normocyte binding protein family in P. knowlesi was published, and manuscripts on the discovery of a PkNBP erythrocyte binding domain, the Pv and Pk RhopH complex, the 11 member Pv MSP3 family, and P. cynomolgi PHIST protein and family are under review for submission. A manuscript defining a novel merozoite apical protein (MAP) is being prepared. This year, extensive transcriptome and proteome data have also been generated and analyzes are underway in preparation for manuscripts and the design of new directions. Further, three reviews have been published and support provided for a study on chimeric vaccine development and testing.

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