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PubMed: 34889942 DOI: 10.1084/jem.20211862
Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge.
J Exp Med 219(2)
Authors: Kerry L Hilligan, Sivaranjani Namasivayam, Chad S Clancy, Danielle O'Mard, Sandra D Oland, Shelly J Robertson, Paul J Baker, Ehydel Castro, Nicole L Garza, Bernard A P Lafont, Reed Johnson, Franca Ronchese, Katrin D Mayer-Barber, Sonja M Best, Alan Sher
Affiliations
- Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
- Immune Cell Biology Programme, Malaghan Institute of Medical Research, Wellington, New Zealand.
- Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT.
- Innate Immunity and Pathogenesis Section, Laboratory of Virology, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT.
- Inflammation and Innate Immunity Unit, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
- SARS-CoV-2 Virology Core, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
Abstract
In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guérin (BCG) has been reported to confer nonspecific resistance to unrelated pulmonary pathogens, a phenomenon attributed to the induction of long-lasting alterations within the myeloid cell compartment. Here, we demonstrate that intravenous, but not subcutaneous, inoculation of BCG protects human-ACE2 transgenic mice against lethal challenge with SARS-CoV-2 (SCV2) and results in reduced viral loads in non-transgenic animals infected with an α variant. The observed increase in host resistance was associated with reductions in SCV2-induced tissue pathology, inflammatory cell recruitment, and cytokine production that multivariate analysis revealed as only partially related to diminished viral load. We propose that this protection stems from BCG-induced alterations in the composition and function of the pulmonary cellular compartment that impact the innate response to the virus and ensuing immunopathology. While intravenous BCG vaccination is not a clinically acceptable practice, our findings provide an experimental model for identifying mechanisms by which nonspecific stimulation of the pulmonary immune response promotes host resistance to SCV2 lethality.
MeSH
Cells, Sars-Cov-2, Vaccines, Administration, Intravenous, Pathology, Viral Load, Vaccination, Severe Acute Respiratory Syndrome-Related Coronavirus
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