Malaria Transmission Blocking Vaccine Discovery

疟疾传播阻断疫苗的发现

• 批准号: 9161590
• 负责人: Patrick Duffy
• 金额: $ 132.04万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9161590
• 关键词: Adjuvant; Aluminum; Animals; Antibodies; Antigens; Area; Blocking Antibodies; Carrier Proteins; Chemicals; Culicidae; Evaluation; Expression Library; Goals; Human; Immune; Immune Sera; Immunity; Individual; Investigation; Malaria; Methods; Parasites; Plasmodium falciparum; Proteins; Recombinant Proteins; Recombinants; ST13 gene; Sampling; Serum; Staging; Surface; Testing; Vaccine Antigen; Vaccines; Work; burden of illness; immunogenicity; interest; malaria transmission; malaria transmission-blocking vaccine; novel; prevent; screening; tool; transmission process; transmission-blocking vaccine

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.

为了开发针对恶性疟原虫和间日疟原虫的传播阻断疫苗 (TBV)，LMIV 重点关注抗原发现，以确定 TBV 的新靶标，以及评估不同平台，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。 抗原发现的重点是使用从自然暴露于疟疾的个体中收集的人血清样本，这些样本似乎产生了有效的免疫力，可以预防配子体血症或阻止寄生虫传播给蚊子，作为识别候选疫苗抗原的工具。具体而言，将具有感兴趣活性的血清样品与缺乏该活性的血清进行比较，以确定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。通过差异筛选鉴定出的重组蛋白随后被制备为免疫原并测试其诱导有效抗配子体或传播阻断抗体的能力。 免疫原性项目的改进集中于来自恶性疟原虫的重组蛋白或其来自间日疟原虫的直系同源物与蛋白载体的化学缀合。正在动物研究中分别评估单体蛋白及其缀合物的功能活性和免疫增强作用，并且正在评估抗血清在蚊子中的传播阻断活性。