BCG immunization mitigates SARS-CoV-2 replication in macaques via monocyte efferocytosis and neutrophil recruitment in lungs.
Abstract
Exposure to Bacillus Calmette-Guerin (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-alpha, 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.
| Authors: | Rahman MA, Goldfarbmuren KC, Sarkis S, Bissa M, Gutowska A, Schifanella L, Moles R, Doster MN, Andersen H, Jethmalani Y, Serebryannyy L, Cardozo T, Lewis MG, Franchini G, |
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| Journal: | JCI Insight;2025Aug08; 10 (15) . doi:10.1172/jci.insight.194633 |
| Year: | 2025 |
| PubMed: | PMID: 40779451 (Go to PubMed) |