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

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。 该项目的广泛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重组蛋白的成员作为候选疟疾疫苗产品。该实验室最初鉴定、表达和表征了这些蛋白质及其作为疟疾候选疫苗的潜力。我们已经鉴定和表征了PvMSP 3家族的其他成员（总共11个基因），并且已经生产了代表每个基因的重组产物用于生物化学表征。重组产物在原核系统中表达，并已用于生产多克隆兔抗血清，识别每个PvMSP 3蛋白。 为了与我们评估人体天然免疫应答的目的保持一致，生产、纯化并测试了代表PvMSP 3 α（PvMSP-3a）蛋白的五种重组产物。最后，在玻利维亚塞米里猴中测试代表PvMSP 3 α（PvMSP-3a）蛋白的相同五种产品的安全性、免疫原性和功效。 这些灵长类动物对间日疟原虫感染易感，可以很好地用作直接攻击模型。虽然攻毒非常可靠，但在支持用于检测间日疟原虫血液阶段疫苗的模型系统时，未检测到保护作用。 这个项目已经有了一个无成本的扩展，这些结果正在准备出版，沿着一篇关于大MSP 3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对这些抗原的自然获得性免疫反应和疫苗诱导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.