Intravenous administration of BCG protects mice against lethal SARS-CoV-2 challenge #MMPMID34889942
Hilligan KL; Namasivayam S; Clancy CS; O'Mard D; Oland SD; Robertson SJ; Baker PJ; Castro E; Garza NL; Lafont BAP; Johnson R; Ronchese F; Mayer-Barber KD; Best SM; Sher A
J Exp Med 2022[Feb]; 219 (2): ä PMID34889942show ga
In addition to providing partial protection against pediatric tuberculosis, vaccination with bacille Calmette-Guerin (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 alpha 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.
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