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。子项目及 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。本研究的具体目的是：1）优化PvMSP-3和PvMSP-9全长和部分基因构建体在细菌或酵母表达系统中的表达，以获得合适的产物，用于进一步测试这些抗原作为疟疾候选疫苗; 2）鉴定PvMSP-3和PvMSP-4中的天然免疫原性B和T细胞表位。9.通过评价巴西疟疾流行地区接触间日疟感染程度不同的个人的现有血液样本; 3）评估小鼠和兔中针对几种含有配制在临床级佐剂中的B和T细胞表位的PvMSP-3和PvMSP-9候选疫苗产生的免疫应答;和4）在非人灵长类动物中测试所选择的PvMSP-3和PvMSP-9候选疫苗制剂的安全性、免疫原性和效力。这项研究的目的是生产多达三种候选产品，可以评估疫苗在新世界猴子中的效力。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。还将在恒河猴中测试最有前途的产品的安全性和免疫原性，以判断在人类临床研究中产生充分反应的潜力。

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.