Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells

• Published in: iScience Vol. 26; no. 10; p. 107733
• Main Authors: 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.
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 20.10.2023; Elsevier
• Subjects: Immune response; Model organism; Virology; Model organism; Immune response; Virology
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2023.107733

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. [Display omitted] •Single-cell transcriptomics of immune cells in BCG-vaccinated, SCV2-infected hamsters•BCG causes the reprogramming of myeloid cells, lymphocytes, and non-immune cells•BCG prevents SCV2-mediated lymphopenia and promotes antigen presentation•BCG vaccination promotes the expansion of plasma cells in SCV2-infected lungs Immune response; Virology; Model organism