Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques
Prevention of tuberculosis infection and disease by local BCG in repeatedly exposed rhesus macaques
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DOI：
10.1038/s41591-018-0319-9
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发表时间：
2019-02-01
期刊：
影响因子：
82.9
通讯作者：
Verreck, Frank A. W.
中科院分区：
文献类型：
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作者：
Dijkman, Karin;Sombroek, Claudia C.;Verreck, Frank A. W.
结核病（TB）仍然是最致命的传染病(1)，广泛使用的卡介苗（Bacillus Calmette-Guerin， BCG）疫苗未能遏制这种流行病。改进的疫苗接种策略可以提供一种具有成本效益的干预措施，打破传播周期并预防抗菌素耐药性（2,3）。对与保护性免疫密切相关的宿主反应的有限了解阻碍了改进结核病疫苗接种方案的发展。因此，在临床疫苗试验之前，评估临床前模型中的新策略以选择最佳候选疫苗仍然是必不可少的。我们之前已经在恒河猴（Macaca mulatta）中证实，在标准皮内注射失败的情况下，肺粘膜卡介苗可减少结核病（4,5）。在这里，我们展示了肺部卡介苗通过使用重复限制剂量结核分枝杆菌攻击模型来预防感染，并确定了多功能T-辅助型17 （T(H)17）细胞、白细胞介素-10和免疫球蛋白a是局部保护性免疫的相关因素。这些发现值得进一步研究粘膜免疫策略及其转化为临床应用，以更有效地预防结核病的传播。
Tuberculosis (TB) remains the deadliest infectious disease(1), and the widely used Bacillus Calmette-Guerin (BCG) vaccine fails to curb the epidemic. An improved vaccination strategy could provide a cost-effective intervention to break the transmission cycle and prevent antimicrobial resistance(2,3). Limited knowledge of the host responses critically involved in protective immunity hampers the development of improved TB vaccination regimens. Therefore, assessment of new strategies in preclinical models to select the best candidate vaccines before clinical vaccine testing remains indispensable. We have previously established in rhesus macaques (Macaca mulatta) that pulmonary mucosal BCG delivery reduces TB disease where standard intradermal injection fails(4,5). Here, we show that pulmonary BCG prevents infection by using a repeated limiting-dose Mycobacterium tuberculosis challenge model and identify polyfunctional T-helper type 17 (T(H)17) cells, interleukin-10 and immunoglobulin A as correlates of local protective immunity. These findings warrant further research into mucosal immunization strategies and their translation to clinical application to more effectively prevent the spread of TB.