Antigen discovery for transmission-blocking vaccines in Plasmodium vivax

项目摘要 对于许多疟疾流行国家为消除疟疾所做的巨大努力，中断疟疾 传播已被认为是最大的挑战之一，这需要采取综合办法。 间日疟原虫是地理上分布最广的人类疟疾，对常规疟疾更具弹性。 由于疟疾的内在生物学原因采取的控制措施，如催眠虫的形成导致疟疾复发和 配子体发育较早，能够在症状出现之前传播。传输- 阻断疫苗(TBV)是一种很有前途的战略，特别适合于消除间日疟的任务。 然而，TBV的研究进展非常缓慢，而对间日疟原虫的TBV研究甚至滞后。 远远落后于恶性疟原虫。由于只有五种寄生虫抗原作为TBV的首选候选抗原， 迫切需要共同努力确定新的TBV抗原。在此应用程序中，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 疫苗设计和投放平台方面的技术和进步。我们的目标是1)发现新的性爱- 通过计算机预测和免疫筛选来分期抗原，并评价其减少传播的活性 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；以及3)评估新的间日疟原虫候选TBV的传播减少活性 转基因伯氏疟原虫和间日疟原虫临床分离株。这些综合研究的结果将有助于 更好地了解疟疾寄生虫性发育和识别新的性期 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.