Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge

J Exp Med. 2022 Feb 7;219(2):e20211862. doi: 10.1084/jem.20211862. Epub 2021 Dec 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Administration, Intravenous
  • Angiotensin-Converting Enzyme 2 / metabolism
  • Animals
  • BCG Vaccine / immunology*
  • COVID-19 / immunology*
  • Chemokines / metabolism
  • Humans
  • Inflammation / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • SARS-CoV-2 / immunology*
  • Viral Load

Substances

  • BCG Vaccine
  • Chemokines
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2