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

iScience (Oct 2023)

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

Journal volume & issue: Vol. 26, no. 10
p. 107733

Abstract

Read online

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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

About the journal

Abstract

Keywords