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沙眼衣原体:细胞生物学、免疫学与疫苗学

Chlamydia trachomatis: Cell biology, immunology and vaccination.

机构信息

Department of Infectious Diseases, Imperial College London, Norfolk Place, London W2 1PG, UK.

出版信息

Vaccine. 2021 May 21;39(22):2965-2975. doi: 10.1016/j.vaccine.2021.03.043. Epub 2021 Mar 24.

Abstract

Chlamydia trachomatis is the causative agent of a highly prevalent sexually transmitted bacterial disease and is associated with a number of severe disease complications. Current therapy options are successful at treating disease, but patients are left without protective immunity and do not benefit the majority asymptomatic patients who do not seek treatment. As such, there is a clear need for a broad acting, protective vaccine that can prevent transmission and protect against symptomatic disease presentation. There are three key elements that underlie successful vaccine development: 1) Chlamydia biology and immune-evasion adaptations, 2) the correlates of protection that prevent disease in natural and experimental infection, 3) reflection upon the evidence provided by previous vaccine attempts. In this review, we give an overview of the unique intra-cellular biology of C. trachomatis and give insight into the dynamic combination of adaptations that allow Chlamydia to subvert host immunity and survive within the cell. We explore the current understanding of chlamydial immunity in animal models and in humans and characterise the key immune correlates of protection against infection. We discuss in detail the specific immune interactions involved in protection, with relevance placed on the CD4+ T lymphocyte and B lymphocyte responses that are key to pathogen clearance. Finally, we provide a timeline of C. trachomatis vaccine research to date and evaluate the successes and failures in development so far. With insight from these three key elements of research, we suggest potential solutions for chlamydial vaccine development and promising avenues for further exploration.

摘要

沙眼衣原体是一种高度流行的性传播细菌病的病原体,与许多严重的疾病并发症有关。目前的治疗方法在治疗疾病方面是成功的,但患者没有保护性免疫,也不能使大多数没有寻求治疗的无症状患者受益。因此,需要一种广谱、保护性疫苗,以预防传播和预防有症状疾病的发生。成功疫苗开发有三个关键要素:1)衣原体生物学和免疫逃避适应;2)预防自然和实验感染疾病的保护相关因素;3)对以前疫苗尝试提供的证据进行反思。在这篇综述中,我们概述了沙眼衣原体独特的细胞内生物学,并深入了解了允许衣原体颠覆宿主免疫并在细胞内存活的适应性动态组合。我们探讨了动物模型和人类中当前对衣原体免疫的理解,并描述了针对感染的关键免疫保护相关因素。我们详细讨论了参与保护的特定免疫相互作用,重点是清除病原体的关键 CD4+T 淋巴细胞和 B 淋巴细胞反应。最后,我们提供了沙眼衣原体疫苗研究的时间线,并评估了迄今为止的开发成功和失败。从这三个研究关键要素中获得的见解,我们提出了针对衣原体疫苗开发的潜在解决方案,并为进一步探索提供了有希望的途径。

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