MOLECULAR ANALYSIS OF PLASMODIUM VIVAX SURFACE ANTIGENS

该子项目是利用 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来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 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，这将有助于开发针对间日疟原虫（人类疟疾的两种最流行的物种之一）的血液阶段裂殖子疫苗。这项研究还有助于加深对恶性疟原虫裂殖子（人类疟疾的另一个主要物种）生物学的了解。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。 其中三个形成一个家族，也可能具有促进慢性化的矛盾作用。该研究旨在调查家族成员的遗传学和多样性方面，以及这可能如何影响这些蛋白质诱导的免疫反应机制。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。了解这些特性对于合理开发潜在的疟疾候选疫苗非常重要。最近的重点是种间比较分析，推定的红细胞粘附结构域的评价，疫苗构建体的开发和表达，以及正在进行的研究，评价自然获得的免疫反应对这些蛋白质。

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. Recent 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.