Mycobacterium bovis bacillus Calmette-Guérin (BCG) immunization still remains the best vaccination strategy available to control the development of active tuberculosis (TB). Protection afforded by BCG vaccination gradually wanes over time and while booster strategies have promise, they remain under development. An alternative approach is to improve BCG efficacy through host-directed therapy. Building upon prior knowledge that blockade of interleukin-10 receptor 1 (IL-10R1) during early Mycobacterium tuberculosis (M.tb) infection improves and extends control of M.tb infection in mice, we employed a combined anti-IL-10R1/BCG vaccine strategy. A subcutaneous, single vaccination of BCG/αIL10-R1 increased the numbers of CD4⁺ and CD8⁺ central memory T cells, and reduced TH1 and TH17 cytokine levels in the lung for up to 7 weeks post vaccination. Subsequent M.tb challenge in mice showed both an early (4 week) and sustained long-term (47 week) control of infection, which was associated with increased survival. In contrast, protection of BCG/saline vaccinated mice waned 8 weeks post M.tb infection. Our findings demonstrate that a single and simultaneous vaccination with BCG/αIL10-R1 sustains long-term protection, identifying a promising approach to enhance and extend the current BCG mediated protection against TB.

中文翻译：

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IL-10 受体阻断剂与 BCG 疫苗接种同时进行，可维持小鼠对结核分枝杆菌感染的长期保护

牛分枝杆菌卡介苗 (BCG) 免疫仍然是控制活动性结核病 (TB) 发展的最佳疫苗接种策略。随着时间的推移，BCG 疫苗提供的保护作用逐渐减弱，虽然加强策略有希望，但它们仍在开发中。另一种方法是通过宿主导向疗法提高 BCG 疗效。基于在早期结核分枝杆菌( M.tb ) 感染期间阻断白细胞介素 10 受体 1 (IL-10R1)改善和扩展对小鼠M.tb感染的控制的先验知识，我们采用了联合抗 IL-10R1/BCG疫苗战略。单次皮下接种 BCG/αIL10-R1 可增加 CD4 ⁺的数量和 CD8 ⁺中枢记忆 T 细胞，并在接种疫苗后长达 7 周内降低肺中的 TH1 和 TH17 细胞因子水平。随后对小鼠的M.tb攻击显示感染的早期（4 周）和持续的长期（47 周）控制，这与存活率增加有关。相比之下，在M.tb感染后 8 周，BCG/盐水疫苗接种小鼠的保护作用减弱。我们的研究结果表明，单次同时接种 BCG/αIL10-R1 可维持长期保护，确定了一种有前景的方法来增强和扩展当前 BCG 介导的针对结核病的保护。