PLASMODIUM VIVAX MSP-3 AND MSP-9 AS VACCINE IMMUNOGENS

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。 该项目的长期目标是开发间日疟原虫裂殖子表面蛋白-3(PvMSP-3)和PvMSP-9重组蛋白作为候选疟疾疫苗产品。该实验室最初识别、表达和表征了这些蛋白质及其作为疟疾候选疫苗的潜力。我们已经鉴定和鉴定了PvMSP3家族的其他成员(共11个基因)，并生产了代表每个基因的重组产品用于生化鉴定。重组产物在原核系统中表达，并用于制备识别PvMSP3蛋白的多克隆兔抗血清。 为了评估人类的天然免疫应答，我们制备了5种代表PvMSP3α(PvMSP-3a)蛋白的重组产物，并进行了纯化和检测。最后，代表PvMSP3α(PvMSP-3a)蛋白的五种产物在赛米里猕猴身上进行了安全性、免疫原性和有效性测试。这些灵长类动物对间日疟原虫感染很敏感，可以很好地作为直接挑战的模型。虽然挑战是非常可靠的，但为了支持间日疟原虫血液期疫苗测试的模型系统，没有检测到保护作用。该项目已经免费延长，这些结果正在准备发表，同时还准备发表一篇关于MSP3大家族的基因和蛋白质表达的论文。 巴西和巴布亚新几内亚的合作者也正在完成关于自然获得和疫苗诱导的对这些抗原的免疫反应的其他研究。

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 broad long-term objective of this project has been to develop members of the Plasmodium vivax merozoite surface protein-3 (PvMSP-3) and PvMSP-9 recombinant proteins as candidate malaria vaccine products. This laboratory originally identified, expressed, and characterized these proteins and their potential as malaria vaccine candidates. We have identified and characterized additional members of the PvMSP3 family (total of eleven genes) and recombinant products representing each gene have been produced for biochemical characterization. The recombinant products were expressed in a prokaryotic system and have been used to produce polyclonal rabbit antisera which recognize each PvMSP3 protein. In keeping with our objective to evaluate the native immune response in humans, five recombinant products representing the PvMSP3 alpha (PvMSP-3a) protein were produced, purified and tested. Finally, the same five products representing the PvMSP3 alpha (PvMSP-3a) protein were tested for safety, immunogenicity and efficacy in Saimiri boliviensis monkeys. These primates are susceptible to P. vivax infections and can serve very well as a direct challenge model. While the challenge was very reliable, in support of the model system for testing of P. vivax blood stage vaccines, no protection was detected. This project has had a no cost extension, and these results are being prepared for publication, along with a paper on the gene and protein expression of the large MSP3 family. Additional studies on the naturally acquired and vaccine induced immune response to these antigens are also being completed by collaborators in Brazil and Papua New Guinea.