Antigen discovery for transmission-blocking vaccines in Plasmodium vivax

项目摘要 感谢许多疟疾流行国家为消灭疟疾所做的巨大努力， 传播被认为是最大的挑战之一，需要采取综合办法。 间日疟原虫是地理分布最广的人类疟疾， 疟疾控制措施，由于其内在的生物学，如催眠虫形成负责复发， 早期配子体发育，使症状出现前的传播。变速器- 阻断疫苗（TBV）是特别适合于消灭间日疟的任务的有希望的策略。 然而，TBV的研究进展缓慢，而间日疟原虫的TBV研究更是滞后 远远落后于恶性疟原虫。由于只有五种寄生虫抗原作为最佳TBV候选物， 迫切需要协同努力来鉴定新的TBV抗原。在本申请中，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输送平台的进步。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，并评价其降低传播活性 在伯氏疟原虫中; 2）评估针对受精前和受精后的TBV组合策略 抗原;和3）使用以下方法评估新的TBV候选物对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。这些全面研究的结果将有助于 更好地了解疟疾寄生虫的性发育和确定新的性阶段 用于TBV开发管道的抗原。

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.