MOLECULAR ANALYSIS OF PLASMODIUM VIVAX SURFACE ANTIGENS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. The long term objective of this project is to analyse and understand structurally and functionally the molecular make-up of Plasmodium vivax merozoites. This knowledge will identify and characterize proteins that may serve as important vivax malaria vaccine candidates or targets of anti-malaria drug interventions. Plasmodium vivax is a highly predominant malaria species, causing 80 million cases or more of malaria each year and major socioeconomic public health ramifications worldwide. Nevertheless, P. vivax is under investigated in part because it cannot be cultured reliably long term in vitro. Specialized expertise and non human primate resources are therefore required for in depth laboratory investigations on this human parasite species. Experimental models using P. vivax parasites and the related simian malaria species P. knowlesi and P. cynomolgi in non-human primates are fundamental to this research program. This year, studies focused on confirming that 10 of 11 P. vivax (Sal I) msp3 genes are expressed as merozoite surface proteins in an infection, and that surprisingly one of these may encode a novel merozoite apical localized protein. Other efforts focused on developing and testing a series of constructs to establish transfection systems for studies of P. vivax. Additionally, parasite stocks of P. vivax were generated from Saimiri boliviensis monkey infections and processed for specific proteomic and cell biological experiments. This research capitalizes extensively on the recent availability of Plasmodium genome databases, utilizing bioinformatics, microarrays, proteomics, genetic manipulation strategies, high resolution imaging capabilities, functional adhesion and invasion assays, immunochemical methods and cell biological technologies.