Key Points Intradermal BCG vaccination cannot protect cynomolgus macaques against pulmonary TB. Extrapulmonary TB is strongly controlled in intradermal BCG–vaccinated monkeys. Recently, the efficacy of Mycobacterium bovis bacillus Calmette–Guérin (BCG) vaccination is being reassessed in accordance with the achievements of clinical tuberculosis (TB) vaccine research. However, the mechanisms ultimately determining the success or failure of BCG vaccination to prevent pulmonary TB remain poorly understood. In this study, we analyzed the protective effects of intradermal BCG vaccination by using specific pathogen–free cynomolgus macaques of Asian origin that were intradermally vaccinated with BCG (Tokyo strain) followed by Mycobacterium tuberculosis (Erdman strain) infection. Intradermal BCG administration generated TB Ag-specific multifunctional CD4 T cell responses in peripheral blood and bronchoalveolar lavage and almost completely protected against the development of TB pathogenesis with aggravation of clinical parameters and high levels of bacterial burdens in extrapulmonary organs. However, interestingly, there were no differences in bacterial quantitation and pathology of extensive granulomas in the lungs between BCG-vaccinated monkeys and control animals. These results indicated that the changes in clinical parameters, immunological responses, and quantitative gross pathology that are used routinely to determine the efficacy of TB vaccines in nonhuman primate models might not correlate with the bacterial burden and histopathological score in the lung as measured in this study.

中文翻译：

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皮内接种卡介苗-Guérin 疫苗可有效预防食蟹猴的肺外结核病，但不会预防肺部感染

要点 皮内接种卡介苗不能保护食蟹猴免受肺结核。在皮内注射 BCG 疫苗的猴子中，肺外结核病得到了很好的控制。最近，根据临床结核病（TB）疫苗研究的成果，正在重新评估牛分枝杆菌卡介苗（BCG）疫苗接种的功效。然而，最终决定 BCG 疫苗接种成功或失败的机制仍然知之甚少。在这项研究中，我们通过使用皮内接种 BCG（东京株）和结核分枝杆菌（Erdman 株）感染的亚洲血统无特定病原体的食蟹猴来分析皮内接种 BCG 的保护作用。皮内注射 BCG 在外周血和支气管肺泡灌洗液中产生了 TB Ag 特异性多功能 CD4 T 细胞反应，并且几乎完全防止了随着临床参数恶化和肺外器官细菌负荷增加而导致的 TB 发病机制的发展。然而，有趣的是，在接种 BCG 的猴子和对照动物之间，肺部广泛肉芽肿的细菌定量和病理学没有差异。这些结果表明，常规用于确定非人灵长类动物模型中结核病疫苗效力的临床参数、免疫反应和定量大体病理学的变化可能与本研究中测量的肺部细菌负荷和组织病理学评分无关.