MOLECULAR ANALYSIS OF PLASMODIUM VIVAX SURFACE ANTIGENS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这项研究的长期目标是提供基本的分子生物学和免疫生物学信息，以支持针对间日疟原虫（人类疟疾的两种最流行的物种之一）的血液阶段疫苗的开发。这项研究还有助于加深对恶性疟原虫生物学的了解，恶性疟原虫是人类疟疾的另一个主要物种。感染恒河猴的相关非人灵长类疟疾P. cynomolgi，P. coatneyi和P. knowlesi是这些研究的极好模型。该项目需要表征几种疟原虫裂殖子蛋白和编码它们的基因，重点是1）在裂殖子侵入红细胞的受体介导的过程中具有明显的直接或间接功能的分子，和2）可能通过刺激抗间日疟原虫免疫应答而在影响间日疟原虫和人类之间的免疫生物学关系中具有作用的分子。 协调使用体外裂殖子侵入和附着测定、免疫电子显微术、基因敲除技术、确定的抗体和重组DNA试剂以及使用猿猴疟疾模型，有助于精确测定和澄清所研究的裂殖子蛋白的位置、功能、结构和可能的相互关系。今年，我们发表了关于在P. knowlesi中鉴定正常细胞结合蛋白家族的报告，并且正在审查提交关于发现PkNBP红细胞结合结构域、Pv和Pk RhopH复合物、11个成员的Pv MSP 3家族以及P. cynomolgi PHIST蛋白和家族的手稿。一个定义新的裂殖子顶端蛋白（MAP）的手稿正在准备中。 今年，还生成了大量的转录组和蛋白质组数据，并正在进行分析，为手稿和新方向的设计做准备。此外，已经发表了三篇综述，并为嵌合疫苗开发和测试的研究提供了支持。

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.