The primary long term objective of this proposed research is to provide basic 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. Accordingly, investigations will be carried out to continue the identification and characterization of P. vivax merozoite proteins that 1) have an apparent function in the process of merozoite invasion of erythrocytes, and 2) likely affect the immunobiological relationship of P. vivax and man by stimulating an anti- P. vivax immune response. Specifically, proteins will be studied that comprise the organized surface coat of the merozoites, or make up some aspect of their internal or external apical pole. A number of these proteins bind with receptor-like specificity to erythrocytes, and therefore likely have direct role in the initial molecular events of invasion. The genes encoding such merozoite proteins have been, or will be isolated from cDNA and genomic DNA libraries. Their deduced protein sequences will be determined by DNA sequence analysis and investigated to study their putative structures and homologies to other known proteins, in order to assess which regions may serve functions vital to the parasite. Putative functional domains will be produced as peptides, or gene segments encoding defined regions will be expressed as antigens for the production of polyclonal immune sera or monoclonal antibodies. These reagents will aid in experiments designed to determine and clarify the localization(s), function(s), and structure(s) of the P. vivax merozoite proteins under investigation, and the possible interactive relationship(s) with each other or with components of the host red blood cell membrane. In addition, immuno-electron microscopic studies will use these reagents and various inhibitors of motility in order to more precisely define each step in the actual process of merozoite invasion.
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