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

Abstract

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.

• Authors: Alok K Singh, Rulin Wang, Kara A Lombardo, Monali Praharaj, C Korin Bullen, Peter Um, Manish Gupta, Geetha Srikrishna, Stephanie Davis, Oliver Komm, Peter B Illei, Alvaro A Ordonez, Melissa Bahr, Joy Huang, Anuj Gupta, Kevin J Psoter, Patrick S Creisher, Maggie Li, Andrew Pekosz, Sabra L Klein, Sanjay K Jain, Trinity J Bivalacqua, Srinivasan Yegnasubramanian, William R Bishai
• Journal: iScience (iScience) Vol. 26 Issue 10 Pg. 107733 (Oct 20 2023) ISSN: 2589-0042 [Electronic] United States
• PMID: 37674985 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors.