MOLECULAR ANALYSIS OF PLASMODIUM VIVAX SURFACE ANTIGENS

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，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（两种最流行的人类疟疾之一）的血期merozoite疫苗。这项研究也与增加对恶性疟原虫（人类疟疾的另一个主要物种）的生物学认识有关。感染恒河猴的相关非人类灵长类动物cynomolgi、P. coatneyi和P. knowlesi是这些研究的优秀模型。本项目需要对几种疟原虫分裂子蛋白及其编码基因进行表征，重点关注1)在受体介导的分裂子侵入红细胞过程中具有明显的直接或间接功能的分子，2)可能通过刺激抗p而影响间日疟原虫与人之间的免疫生物学关系。间日免疫反应。其中的三个组成了一个家庭，这个家庭也可能具有促进慢性疾病的矛盾作用。该研究旨在调查家族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。协调使用体外merozoite侵袭和附着试验，免疫电子显微镜，基因敲除技术，定义抗体和重组DNA试剂，以及使用类人猿疟疾模型，有助于精确确定和澄清所研究的merozoite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。在过去的一年里，特别强调的是种间比较分析，对假定的红细胞粘附结构域的评估，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质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. This past year special 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.