ABSTRACT

Introduction

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.

Areas covered

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.

Expert opinion

Candidates targeting P. falciparum zygote surface antigen Pfs25, and its P. vivax 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.

中文翻译：

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阻断传播的疫苗：利用群体免疫消除疟疾

摘要

介绍

阻断传播的疫苗 (TBV) 通过针对蚊子性阶段寄生虫（生命周期的瓶颈）来防止疟疾的社区传播，并将用于消除计划。TBV 依靠群体免疫来减少蚊子感染，从而减少疫苗接受者和非接受者的新感染，但一旦个体受到传染性蚊虫叮咬，临床开发变得复杂，则无法提供保护。

覆盖区域

在这里，我们描述了 TBV 背后的概念和生物学，并提供了领先疫苗候选抗原临床开发的最新信息。搜索词“疟疾疫苗”、“性阶段”、“传播阻断疫苗”、“VIMT”和“SSM-VIMT”被用于 PubMed 查询以识别相关文献。

专家意见

靶向恶性疟原虫受精卵表面抗原 Pfs25 及其间日疟原虫直系同源物 Pvs25 的候选物在人体中诱导功能活性，从而在替代试验中减少蚊子感染，但需要增加耐用性才能在该领域使用。分别针对配子表面抗原 Pfs230 和 Pfs48/45 的候选药物正在进行或接近临床试验。正在探索纳米颗粒平台和佐剂以增强免疫原性。功效试验需要特殊考虑，例如整群随机设计来衡量降低人类和蚊子感染率的群体免疫力，同时将人类和蚊子的活动作为混杂因素处理。