MOLECULAR ANALYSIS OF PLASMODIUM VIVAX SURFACE ANTIGENS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 这项研究的长期目标是提供基本的基本分子生物学和免疫生物学信息，有助于开发针对间日疟原虫的血液期裂殖子疫苗，间日疟原虫是人类疟疾最流行的两个物种之一。这项研究也有助于增进对恶性疟原虫裂殖子生物学的了解，恶性疟原虫裂殖子是人类疟疾的另一个主要物种。感染恒河猴的相关非人类灵长类疟原虫食蟹猴疟原虫、柯氏疟原虫和诺氏疟原虫是这些研究的极佳模型。该项目需要对几种疟原虫裂殖子蛋白及其编码基因进行表征，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，以及2)可能通过刺激抗间日疟原虫而影响间日疟原虫与人类之间的免疫生物学关系的分子。间日疟原虫免疫反应。其中三个人组成的家庭可能还具有促进慢性病的自相矛盾的作用。这项研究旨在调查这些家庭成员的遗传和多样性方面，以及这可能如何影响这些蛋白质诱导的免疫反应机制。配合使用体外裂殖子侵袭和附着分析、免疫电子显微镜、基因敲除技术、确定的抗体和重组DNA试剂，以及使用猴疟疾模型，有助于精确确定和澄清所研究的裂殖子蛋白的位置、功能、结构和可能的相互作用关系。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。最近的重点是物种间的比较分析，对推测的红细胞粘附域的评估，疫苗结构的开发和表达，以及正在进行的评估针对这些蛋白产生的自然获得性免疫反应的研究。

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.