Laboratory of Malaria Immunology and Vaccinology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Expert Rev Vaccines. 2021 Feb;20(2):185-198. doi: 10.1080/14760584.2021.1878028. Epub 2021 Jan 31.
Transmission-blocking vaccines (TBV) prevent community spread of malaria by targeting mosquito sexual stage parasites, a life-cycle bottleneck, and will be used in elimination programs. TBV rely on herd immunity to reduce mosquito infections and thereby new infections in both vaccine recipients and non-recipients, but do not provide protection once an individual receives an infectious mosquito bite which complicates clinical development.
Here, we describe the concept and biology behind TBV, and we provide an update on clinical development of the leading vaccine candidate antigens. Search terms 'malaria vaccine,' 'sexual stages,' 'transmission blocking vaccine,' 'VIMT' and 'SSM-VIMT' were used for PubMed queries to identify relevant literature.
Candidates targeting zygote surface antigen Pfs25, and its orthologue Pvs25, induced functional activity in humans that reduced mosquito infection in surrogate assays, but require increased durability to be useful in the field. Candidates targeting gamete surface antigens Pfs230 and Pfs48/45, respectively, are in or nearing clinical trials. Nanoparticle platforms and adjuvants are being explored to enhance immunogenicity. Efficacy trials require special considerations, such as cluster-randomized designs to measure herd immunity that reduces human and mosquito infection rates, while addressing human and mosquito movements as confounding factors.
传播阻断疫苗（TBV）通过针对蚊媒的有性阶段寄生虫（生命周期的瓶颈）来预防疟疾的社区传播，将用于消除疟疾计划。TBV 依赖群体免疫来减少蚊子感染，从而减少疫苗接种者和非接种者的新感染，但在个体被感染性蚊子叮咬后，疫苗不会提供保护，这使得临床开发变得复杂。
本文描述了 TBV 的概念和生物学原理，并更新了领先的疫苗候选抗原的临床开发情况。使用“疟疾疫苗”、“有性阶段”、“传播阻断疫苗”、“VIMT”和“SSM-VIMT”等术语在 PubMed 上进行查询，以确定相关文献。
针对合子表面抗原 Pfs25 及其同源物 Pvs25 的候选物在人体中诱导了具有功能活性的反应，可降低替代试验中的蚊子感染率，但需要提高耐久性才能在现场发挥作用。针对配子表面抗原 Pfs230 和 Pfs48/45 的候选物分别处于或接近临床试验阶段。正在探索纳米颗粒平台和佐剂来增强免疫原性。疗效试验需要特殊考虑，例如采用集群随机设计来衡量降低人类和蚊子感染率的群体免疫，同时解决人类和蚊子的移动性作为混杂因素。
