Malaria Transmission Blocking Vaccine Discovery

为了开发针对恶性疟原虫和间日疟原虫的传播阻断疫苗（transmission blocking vaccine，TBV），LMIV专注于抗原发现以鉴定TBV的新靶点，以及评估不同的平台，特别是蛋白质-蛋白质缀合以增强已知抗原的免疫原性。 抗原发现集中于使用从自然暴露于疟疾的个体收集的人血清样品，并且这些人似乎产生了有效的免疫力，可以防止配子体血症，或者阻断寄生虫传播给蚊子，作为鉴定候选疫苗抗原的工具。具体地，将具有感兴趣的活性的血清样品与缺乏该活性的血清比较它们在恶性疟原虫表达文库中选择或识别单个重组蛋白构建体的能力。然后将通过差异筛选鉴定的重组蛋白制备为免疫原，并测试它们诱导有效的抗配子体抗体或传递阻断抗体的能力。 免疫原性的改进项目集中于将来自恶性疟原虫的重组蛋白或其来自间日疟原虫的直向同源物化学缀合至蛋白载体。在动物研究中分别评价单体蛋白及其缀合物的功能活性和免疫增强，并且评价抗血清在蚊子中的传播阻断活性。

In order to develop a transmission blocking vaccine (TBV) against P. falciparum and P. vivax, LMIV has focused on antigen discovery to identify new targets of TBV, as well as evaluation of different platforms particularly protein-protein conjugation to enhance immunogenicity of known antigens. Antigen discovery has focused on using human serum samples collected from individuals that are naturally exposed to malaria, and who appear to develop effective immunity that prevents gametocytemia, or that blocks parasite transmission to mosquitoes, as tools to identify candidate vaccine antigens. Specifically, serum samples that have activity of interest, are compared to sera that lack this activity, for their ability to select or recognize individual recombinant proteins constructs in P. falciparum expression libraries. Recombinant proteins identified through differential screening are tyhen prepared as immunogens and tested for their ability to induce effective anti-gametocyte or transmission blocking antibodies. Improvement of immunogenicity projects have focused on chemical conjugation of recombinant proteins from P. falciparum or their orthologues from P. vivax, to protein carriers. The monomeric proteins and conjugates thereof are being evaluated in animal studies for functional activity and immune enhancement, respectively and the antisera are being evaluated for transmission blocking activities in mosquitoes.