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Prevention of tuberculosis in macaques after intravenous BCG immunization

机译：静脉卡介苗免疫后预防猕猴结核

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Mycobacterium tuberculosis (Mtb) is the leading cause of death from infection worldwide(1). The only available vaccine, BCG (Bacillus Calmette-Guerin), is given intradermally and has variable efficacy against pulmonary tuberculosis, the major cause of mortality and disease transmission(1,2). Here we show that intravenous administration of BCG profoundly alters the protective outcome of Mtb challenge in non-human primates (Macaca mulatta). Compared with intradermal or aerosol delivery, intravenous immunization induced substantially more antigen-responsive CD4 and CD8 T cell responses in blood, spleen, bronchoalveolar lavage and lung lymph nodes. Moreover, intravenous immunization induced a high frequency of antigen-responsive T cells across all lung parenchymal tissues. Six months after BCG vaccination, macaques were challenged with virulent Mtb. Notably, nine out of ten macaques that received intravenous BCG vaccination were highly protected, with six macaques showing no detectable levels of infection, as determined by positron emission tomography-computed tomography imaging, mycobacterial growth, pathology and granuloma formation. The finding that intravenous BCG prevents or substantially limits Mtb infection in highly susceptible rhesus macaques has important implications for vaccine delivery and clinical development, and provides a model for defining immune correlates and mechanisms of vaccine-elicited protection against tuberculosis.
机译：结核分枝杆菌（Mtb）是全世界感染死亡的主要原因（1）。唯一可用的疫苗BCG（卡介苗芽孢杆菌（Bacillus Calmette-Guerin））是皮内注射的，对肺结核（死亡率和疾病传播的主要原因）具有可变的疗效（1,2）。在这里，我们显示静脉注射BCG可以深刻改变非人类灵长类动物（猕猴）中Mtb攻击的保护结果。与皮内或气雾剂递送相比，静脉内免疫在血液，脾脏，支气管肺泡灌洗和肺淋巴结中诱导更多的抗原反应性CD4和CD8 T细胞反应。此外，静脉免疫在所有肺实质组织中诱导了高频率的抗原反应性T细胞。卡介苗接种六个月后，猕猴接受了有毒的Mtb攻击。值得注意的是，接受了BCG静脉注射的十只猕猴中，有九只受到了高度保护，通过正电子发射断层扫描，计算机断层摄影成像，分枝杆菌生长，病理学和肉芽肿形成，确定了六只猕猴没有可检测到的感染水平。静脉注射BCG预防或大大限制了高度易感恒河猴的Mtb感染的发现对疫苗输送和临床开发具有重要意义，并为定义免疫相关性和疫苗引发的抗结核保护机制提供了模型。

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