Persistent BCG bacilli perpetuate CD4 T effector memory and optimal protection against tuberculosis
Persistent BCG bacilli perpetuate CD4 T effector memory and optimal protection against tuberculosis
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DOI：
10.1016/j.vaccine.2014.10.041
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发表时间：
2014-12-05
期刊：
影响因子：
5.5
通讯作者：
Hogarth, Philip J.
中科院分区：
文献类型：
--
作者：
Kaveh, Daryan A.;Garcia-Pelayo, M. Carmen;Hogarth, Philip J.
结核病（TB）仍然是人类和动物最重要的传染病之一，唯一可用的疫苗（BCG）需要紧急更换或改进。为了促进这一点，需要进一步了解卡介苗诱导的保护机制。作为减毒活疫苗，卡介苗在宿主体内的持续存在可能是一个关键机制。我们利用已建立的小鼠模型，研究了接种疫苗后卡介苗的长期持续存在以及对诱导的免疫反应和保护的影响。我们试图确定先前鉴定的 BCG 特异性 CD4 T-EM 细胞是否代表频率相对较高的真正的长寿记忆细胞，或者是长期持久性 BCG 疫苗杆菌持续引发的结果。通过清除持久性杆菌，我们比较了在存在和不存在这些持久性疫苗杆菌的情况下的免疫反应（脾和肺 CD4：产生细胞因子的 T 效应器/T-EM；TCR 特异性）和 BCG 诱导的保护。活的 BCG 杆菌在疫苗接种后持续存在至少 16 个月，与特定的 CD4 T 效应子/T-EM 和四聚体特异性反应相关。清除这些杆菌会消除所有 BCG 特异性 CD4 T 细胞，同时仅将保护作用降低 1 log(10)。BCG 可能会诱导两种附加的免疫机制：(i) 依赖于活杆菌和 T-EM 的存在；这些数据对于替代结核疫苗的合理产生以及动物模型中卡介苗诱导免疫的解释具有重要意义。皇冠版权所有 (C) 2014 由 Elsevier Ltd 出版。
Tuberculosis (TB) remains one of the most important infectious diseases of man and animals, and the only available vaccine (BCG) requires urgent replacement or improvement. To facilitate this, the protective mechanisms induced by BCG require further understanding. As a live attenuated vaccine, persistence of BCG bacilli in the host may be a crucial mechanism.We have investigated the long term persistence of BCG following vaccination and the influence on the induced immune response and protection, using an established murine model. We sought to establish whether previously identified BCG-specific CD4 T-EM cells represent genuine long-lived memory cells of a relatively high frequency, or are a consequence of continual priming by chronically persistent BCG vaccine bacilli.By clearing persistent bacilli, we have compared immune responses (spleen and lung CD4: cytokine producing T effector/T-EM; TCR-specific) and BCG-induced protection, in the presence and absence of these persisting vaccine bacilli. Viable BCG bacilli persisted for at least 16 months post-vaccination, associated with specific CD4 T effector/T-EM and tetramer-specific responses. Clearing these bacilli abrogated all BCG-specific CD4 T cells whilst only reducing protection by 1 log(10).BCG may induce two additive mechanisms of immunity: (i) dependant on the presence of viable bacilli and T-EM; and (ii) independent of these factors.These data have crucial implications on the rational generation of replacement TB vaccines, and the interpretation of BCG induced immunity in animal models. Crown Copyright (C) 2014 Published by Elsevier Ltd.