Singh Alok K, Wang Rulin, Lombardo Kara A, Praharaj Monali, Bullen C Korin, Um Peter, Gupta Manish, Srikrishna Geetha, Davis Stephanie, Komm Oliver, Illei Peter B, Ordonez Alvaro A, Bahr Melissa, Huang Joy, Gupta Anuj, Psoter Kevin J, Creisher Patrick S, Li Maggie, Pekosz Andrew, Klein Sabra L, Jain Sanjay K, Bivalacqua Trinity J, Yegnasubramanian Srinivasan, Bishai William R
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA.
Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA.
iScience. 2023 Aug 24;26(10):107733. doi: 10.1016/j.isci.2023.107733. eCollection 2023 Oct 20.
Bacillus Calmette-Guérin (BCG) confers heterologous immune protection against viral infections and has been proposed as vaccine against SARS-CoV-2 (SCV2). Here, we tested intravenous BCG vaccination against COVID-19 using the golden Syrian hamster model. BCG vaccination conferred a modest reduction on lung SCV2 viral load, bronchopneumonia scores, and weight loss, accompanied by a reversal of SCV2-mediated T cell lymphopenia, and reduced lung granulocytes. BCG uniquely recruited immunoglobulin-producing plasma cells to the lung suggesting accelerated local antibody production. BCG vaccination also recruited elevated levels of Th1, Th17, Treg, CTLs, and Tmem cells, with a transcriptional shift away from exhaustion markers and toward antigen presentation and repair. Similarly, BCG enhanced recruitment of alveolar macrophages and reduced key interstitial macrophage subsets, that show reduced IFN-associated gene expression. Our observations indicate that BCG vaccination protects against SCV2 immunopathology by promoting early lung immunoglobulin production and immunotolerizing transcriptional patterns among key myeloid and lymphoid populations.
卡介苗（BCG）可提供针对病毒感染的异源免疫保护，并且已被提议作为针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2，SCV2）的疫苗。在此，我们使用金黄叙利亚仓鼠模型测试了静脉注射卡介苗对2019冠状病毒病（COVID-19）的预防效果。卡介苗接种使肺部SCV2病毒载量、支气管肺炎评分和体重减轻有适度降低，同时逆转了SCV2介导的T细胞淋巴细胞减少，并减少了肺部粒细胞。卡介苗独特地将产生免疫球蛋白的浆细胞募集到肺部，表明局部抗体产生加速。卡介苗接种还募集了更高水平的辅助性T细胞1（Th1）、辅助性T细胞17（Th17）、调节性T细胞（Treg）、细胞毒性T淋巴细胞（CTL）和记忆性T细胞（Tmem），转录从耗竭标志物转向抗原呈递和修复。同样，卡介苗增强了肺泡巨噬细胞的募集，并减少了关键的间质巨噬细胞亚群，这些亚群显示干扰素相关基因表达降低。我们的观察结果表明，卡介苗接种通过促进肺部早期免疫球蛋白产生以及使关键髓样和淋巴样细胞群之间的免疫耐受转录模式，来预防SCV2免疫病理学。
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