Antigen discovery for transmission-blocking vaccines in Plasmodium vivax

间日疟原虫传播阻断疫苗的抗原发现

• 批准号: 10388106
• 负责人: yaming Cao
• 金额: $ 13.5万
• 依托单位: CHINA MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-04-06 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10388106
• 关键词: Adjuvant; Animals; Antibodies; Antibody Response; Antigen Targeting; Antigens; Asian; Avidity; B-Lymphocyte Epitopes; Biological Assay; Biology; Blood; Cell-Free System; Cells; Chimera organism; Clinical; Combined Vaccines; Complex; Culicidae; Data; Development; Epitopes; Evaluation; Face; Fertilization; Gene Expression Profile; Geography; Germ Cells; Goals; Human; Huntingtin-Associated protein 1; Immunologics; Incidence; Infection; Interruption; Investments; Libraries; Life Cycle Stages; Malaria; Measures; Membrane; Midgut; Mining; Modeling; Morphology; Mus; Oocysts; Orthologous Gene; Parasites; Pathway interactions; Patients; Plasmodium; Plasmodium berghei; Plasmodium falciparum; Plasmodium vivax; Population Study; Protein Array; Protein Microchips; Proteins; Proteome; Recording of previous events; Relapse; Rodent; ST13 gene; Sexual Development; Site; Symptoms; System; Technology; Testing; Transgenic Organisms; Vaccine Antigen; Vaccine Design; Vaccine Research; Vaccines; Validation; Virus-like particle; Vivax Malaria; Wheat; base; design; feeding; fertilization antigen; genome-wide; improved; in silico; innovation; malaria transmission; malaria transmission-blocking vaccine; nanoparticle; novel vaccines; polyclonal antibody; prevent; protein expression; screening; southeast Asian; transcriptome; transmission process; transmission-blocking vaccine; trend; vaccine candidate; vaccine delivery; vaccine development; vaccine trial; vaccine-induced antibodies; vector mosquito; zygote

Project Summary For the immense undertaking by many malaria-endemic nations to eliminate malaria, interruption of malaria transmission has been recognized as one of the greatest challenges, which requires integrated approaches. Plasmodium vivax, the most geographically widespread human malaria, is more resilient to conventional malaria control measures due to its intrinsic biology such as hypnozoite formation responsible for relapses and earlier gametocyte development enabling transmission before manifestation of symptoms. Transmission- blocking vaccines (TBVs) are a promising strategy especially suited for the task of elimination of vivax malaria. However, the progress in TBV development has been very slow, whereas TBV research for P. vivax lags even far behind that for Plasmodium falciparum. With only five parasite antigens as the top TBV candidates, concerted efforts to identify new TBV antigens are urgently needed. In this application, we propose to use an innovative antigen discovery pathway taking advantage of new protein expression and immunoscreening technologies, and advancement in vaccine design and delivery platforms. We aim to 1) discover new sexual- stage antigens by in silico prediction and immunoscreening, and evaluate their transmission reducing activities in Plasmodium berghei; 2) evaluate a TBV combination strategy targeting both pre- and post-fertilization antigens; and 3) assess the transmission reducing activities of new TBV candidates for P. vivax using transgenic P. berghei and clinical P. vivax isolates. Results from these comprehensive studies will contribute to a better understanding of sexual development in malaria parasites and identification of new sexual-stage antigens for the TBV development pipeline.

项目概要 感谢许多疟疾流行国家为消除疟疾、阻断疟疾所做的巨大努力 传输被认为是最大的挑战之一，需要采取综合方法。 间日疟原虫是地理分布最广的人类疟疾，对传统疟疾的抵抗力更强 疟疾控制措施归因于其固有的生物学特性，例如导致复发的催眠体形成和 较早的配子体发育能够在症状出现之前进行传播。传播- 阻断疫苗（TBV）是一种很有前景的策略，特别适合消除间日疟疾。 然而，TBV的开发进展非常缓慢，而间日疟原虫的TBV研究甚至滞后 远远落后于恶性疟原虫。只有五种寄生虫抗原是 TBV 的最佳候选者， 迫切需要共同努力鉴定新的结核病抗原。在此应用中，我们建议使用 利用新蛋白表达和免疫筛选的创新抗原发现途径 技术以及疫苗设计和交付平台的进步。我们的目标是 1）发现新的性- 通过计算机预测和免疫筛选对抗原进行分期，并评估其减少传播的活性 伯氏疟原虫； 2) 评估针对受精前和受精后的 TBV 组合策略 抗原； 3) 使用新的 TBV 候选物评估间日疟原虫的传播减少活性 转基因伯氏疟原虫和临床间日疟原虫分离株。这些综合研究的结果将有助于 更好地了解疟疾寄生虫的性发育并确定新的性阶段 TBV 开发管线的抗原。