Intravenous BCG vaccination reduces SARS-CoV-2 severity and promotes extensive reprogramming of lung immune cells
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
Affiliations
Alok K. Singh
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA
Rulin Wang
Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
Kara A. Lombardo
Johns Hopkins University, School of Medicine, Department of Urology, Baltimore, MD, USA
Monali Praharaj
Bloomberg∼Kimmel Institute for Cancer Immunotherapy at Johns Hopkins, Baltimore, MD, USA
C. Korin Bullen
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA
Peter Um
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA
Manish Gupta
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA
Geetha Srikrishna
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA
Stephanie Davis
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA
Oliver Komm
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA
Peter B. Illei
Johns Hopkins University, School of Medicine, Department of Pathology, Baltimore, MD, USA
Alvaro A. Ordonez
Johns Hopkins University, School of Medicine, Department of Pediatrics, Division of Infectious Diseases, Baltimore, MD, USA
Melissa Bahr
Johns Hopkins University, School of Medicine, Department of Pediatrics, Division of Infectious Diseases, Baltimore, MD, USA
Joy Huang
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA
Anuj Gupta
Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
Kevin J. Psoter
Johns Hopkins University, School of Medicine, Department of Pediatrics, Division of General Pediatrics, Baltimore, MD, USA
Patrick S. Creisher
Johns Hopkins University, Bloomberg School of Public Health, The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Baltimore, MD, USA
Maggie Li
Johns Hopkins University, Bloomberg School of Public Health, The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Baltimore, MD, USA
Andrew Pekosz
Johns Hopkins University, Bloomberg School of Public Health, The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Baltimore, MD, USA
Sabra L. Klein
Johns Hopkins University, Bloomberg School of Public Health, The W. Harry Feinstone Department of Molecular Microbiology and Immunology, Baltimore, MD, USA
Sanjay K. Jain
Johns Hopkins University, School of Medicine, Department of Pediatrics, Division of Infectious Diseases, Baltimore, MD, USA
Trinity J. Bivalacqua
Perelman School of Medicine at the University of Pennsylvania, Division of Urology, Department of Surgery, Philadelphia, PA, USA
Srinivasan Yegnasubramanian
Sydney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, USA
William R. Bishai
Johns Hopkins University, School of Medicine, Department of Medicine, Center for Tuberculosis Research, Baltimore, MD, USA; Corresponding author
Summary: 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.
