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)和重组蛋白PvMSP-9作为疟疾疫苗候选产品。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。这项研究的具体目的是：1)优化PvMSP-3和PvMSP-9全长和部分基因在细菌或酵母表达系统中的表达，以获得适当的产品，用于进一步测试这些抗原作为疟疾疫苗候选；2)通过评估巴西流行地区不同程度暴露于间日疟原虫的人现有的血液样本，鉴定PvMSP-3和PvMSP-9中的天然免疫原性B和T细胞表位；3)评估针对几种包含临床级佐剂中的B和T细胞表位的PvMSP-3和PvMSP-9候选疫苗在小鼠和兔子中产生的免疫反应；4)在非人类灵长类动物中测试选定的PvMSP-3和PvMSP-9候选疫苗配方的安全性、免疫原性和有效性。这项研究的目的是生产最多三种候选产品，可以评估新世界猴子的疫苗效力。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。最有希望的产品也将在恒河猴身上进行安全性和免疫原性测试，以判断在人类临床研究中产生足够反应的可能性。

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 is to develop 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. The specific aims of the study are to: 1) Optimize the expression of PvMSP-3 and PvMSP-9 full-length and partial gene constructs in bacterial or yeast expression systems to obtain appropriate products for further testing of these antigens as malaria vaccine candidates; 2) Identify natural immunogenic B and T cell epitopes in PvMSP-3 and PvMSP-9 by evaluating currently available blood samples from individuals with different levels of exposure to P. vivax malaria infections in endemic areas of Brazil; 3) Evaluate immune responses in mice and rabbits, generated against several PvMSP-3 and PvMSP-9 candidate vaccine containing B and T cell epitopes formulated in clinical grade adjuvants; and 4) Test the safety, immunogenicity and efficacy of selected PvMSP-3 and PvMSP-9 candidate vaccine formulations in non-human primates. This research aims to produce up to three candidate products that can be evaluated for vaccine efficacy in New World monkeys. These primates are susceptible to P. vivax infections and can serve very well as a direct challenge model. The most promising products will also be tested in rhesus macaques for safety and immunogenicity in order to judge the potential for producing adequate responses in human clinical studies.