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

间日疟原虫 MSP-3 和 MSP-9 作为疫苗免疫原

• 批准号: 8172356
• 负责人: MARY R GALINSKI
• 金额: $ 5.48万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8172356
• 关键词: Antigens; Biochemical; Biological Models; Blood; Brazil; Computer Retrieval of Information on Scientific Projects Database; Family; Funding; Gene Proteins; Genes; Grant; Human; Immune Sera; Immune response; Infection; Institution; Laboratories; Malaria Vaccines; Modeling; Monkeys; Oryctolagus cuniculus; Paper; Papua New Guinea; Plasmodium vivax; Primates; Proteins; Publications; Recombinant Proteins; Recombinants; Research; Research Personnel; Resources; Saimiri; Source; Staging; System; Testing; United States National Institutes of Health; Vaccines; cost; immunogenicity; member; merozoite surface protein; protein expression; safety testing; vaccine candidate

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 该项目的广泛长期目标是将Vivax Merozoite表面蛋白-3（PVMSP-3）和PVMSP-9重组蛋白作为候选疟疾疫苗产品的成员。该实验室最初鉴定出，表达和表征这些蛋白质及其潜力是疟疾疫苗候选物。我们已经确定并表征了PVMSP3家族的其他成员（总共11个基因），并且已经生成了代表每个基因的重组产物用于生化表征。重组产物在原核系统中表达，并已用于产生识别每种PVMSP3蛋白的多克隆兔抗血清。 为了符合我们评估人类中天然免疫反应的目标，产生，纯化和测试，五种代表PVMSP3α（PVMSP-3A）蛋白的重组产物。最后，对代表PVMSP3α（PVMSP-3A）蛋白的相同五种产品进行了测试，以确保安全，免疫原性和疗效。 这些灵长类动物容易受到疟原虫感染的影响，并且可以很好地作为直接挑战模型。虽然挑战非常可靠，但为了支持用于测试维瓦克斯血液阶段疫苗的模型系统，未检测到保护。 该项目已经无需延长成本，并且这些结果正在准备出版，以及有关大型MSP3家族的基因和蛋白质表达的论文。 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也由巴西和巴布亚新几内亚的合作者完成。