Abstract

Introduction: The development of effective vaccines remains a major health priority to combat the global burden of malaria, a life-threatening disease caused by Plasmodium parasites. Transmission-blocking vaccines (TBVs) elicit antibodies that neutralize the sexual stages of the parasite in blood meals ingested by the Anopheles mosquito, interrupting parasite development in the vector host and preventing disease spread to other individuals.

Areas covered: The P. falciparum gametocyte surface antigens Pfs230, Pfs48/45, and Pfs47, the parasite ookinete surface protein Pfs25, and the male gametocyte specific protein PfHAP2 are leading TBV candidates, some of which are in clinical development. The recent expansion of methodology to study monoclonal antibodies isolated directly from humans and animal models, coupled with effective measures for parasite neutralization, has provided unprecedented insight into TBV efficacy and development.

Expert opinion: Available structural and functional data on antigen-monoclonal antibody (Ag-mAb) complexes, as well as epitope classification studies, have identified neutralizing epitopes that may aid vaccine development and improve protection. Here, we review the clinical prospects of TBV candidates, progress in the development of novel vaccine strategies for TBVs, and the impact of structural vaccinology in TBV design.

摘要

简介：开发有效疫苗仍然是应对全球疟疾负担的主要健康重点，疟疾是由疟原虫寄生虫引起的致命性疾病。传播阻断疫苗（TBV）产生的抗体可中和按蚊蚊子摄入的血粉中寄生虫的性阶段，中断载体宿主中的寄生虫发育并防止疾病传播到其他个体。

覆盖的区域：恶性疟原虫配子体表面抗原Pfs230，Pfs48 / 45和Pfs47，寄生虫钩形表面蛋白Pfs25和雄性配子体特异性蛋白PfHAP2是主要的TBV候选物，其中一些正在临床开发中。最近研究方法的扩展，以研究直接从人和动物模型中分离出的单克隆抗体，以及用于寄生虫中和的有效措施，为TBV的功效和发展提供了前所未有的见识。

专家意见：有关抗原单克隆抗体（Ag-mAb）复合物的可用结构和功能数据，以及抗原决定簇分类研究，已经确定了中和抗原决定簇，可以帮助疫苗开发和改善保护作用。在这里，我们回顾了TBV候选物的临床前景，针对TBV的新型疫苗策略的开发进展以及结构疫苗学对TBV设计的影响。