Journal Article Epublish
PubMed: 40779451 DOI: 10.1172/jci.insight.194633
BCG immunization mitigates SARS-CoV-2 replication in macaques via monocyte efferocytosis and neutrophil recruitment in lungs.
JCI Insight 10(15)
Authors: Mohammad Arif Rahman, Katherine C Goldfarbmuren, Sarkis Sarkis, Massimiliano Bissa, Anna Gutowska, Luca Schifanella, Ramona Moles, Melvin N Doster, Hanne Andersen, Yogita Jethmalani, Leonid Serebryannyy, Timothy Cardozo, Mark G Lewis, Genoveffa Franchini
Affiliations
- Animal Models and Retroviral Vaccines Section, Basic Research Laboratory, Center for Cancer Research (CCR), National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, Maryland, USA.
- Advanced Biomedical Computational Science, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA.
- CCR Collaborative Bioinformatics Resource, NCI, NIH, Bethesda, Maryland, USA.
- Bioqual, Rockville, Maryland, USA.
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, USA.
- New York University Grossman School of Medicine, NYU Langone Health, New York, New York, USA.
Abstract
Exposure to Bacillus Calmette-Guérin (BCG) or Canarypox ALVAC/Alum vaccine elicits pro- or antiinflammatory innate responses, respectively. We tested whether prior exposure of macaques to these immunogens protected against SARS-CoV-2 replication in lungs and found more efficient replication control after the pro-inflammatory immunity elicited by BCG. The decreased virus level in lungs was linked to early infiltrates of classical monocytes producing IL-8 with systemic neutrophils, Th2 cells, and Ki67+CD95+CD4+ T cells producing CCR7. At the time of SARS-CoV-2 exposure, BCG-treated animals had higher frequencies of lung infiltrating neutrophils and higher CD14+ cells expressing efferocytosis marker MERTK, responses correlating with decreased SARS-CoV-2 replication in lung. At the same time point, plasma IL-18, TNF-α, TNFSF-10, and VEGFA levels were also higher in the BCG group and correlated with decreased virus replication. Finally, after SARS-CoV-2 exposure, decreased virus replication correlated with neutrophils producing IL-10 and CCR7 preferentially recruited to the lungs of BCG-vaccinated animals. These data point to the importance of the spatiotemporal distribution of functional monocytes and neutrophils in controlling SARS-CoV-2 levels and suggest a central role of monocyte efferocytosis in curbing replication.
MeSH
Neutrophil Infiltration, Cells, Sars-Cov-2, Lung, Immunization, Monocytes, Vaccines, Biomedical Research, Virus Replication, Neutrophils, Viruses, Severe Acute Respiratory Syndrome-Related Coronavirus