BCG immunization mitigates SARS-CoV-2 replication in macaques via monocyte efferocytosis and neutrophil recruitment in lungs
Mohammad Arif Rahman, … , Mark G. Lewis, Genoveffa Franchini
Mohammad Arif Rahman, … , Mark G. Lewis, Genoveffa Franchini
Published August 8, 2025
Citation Information: JCI Insight. 2025;10(15):e194633. https://doi.org/10.1172/jci.insight.194633.
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Research Article Immunology Infectious disease

BCG immunization mitigates SARS-CoV-2 replication in macaques via monocyte efferocytosis and neutrophil recruitment in lungs

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.

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

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Figure 1

Schematic representation of the immunization regimen and replicating viral load in BAL.

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Schematic representation of the immunization regimen and replicating vir...
(A) Thirteen rhesus macaques included in this study were divided into 3 groups: BCG vaccine (n = 4), ALVAC/Alum vaccine (n = 4), and controls (n = 5). BCG vaccine was administered once intradermally (ID), and ALVAC/Alum vaccine was administered twice, 6 weeks apart, intramuscularly (IM). Controls remained untreated until challenge. Nine weeks after last immunization all the animals were exposed to 2019-nCoV/USA-WA1/2020 SARS-CoV-2 virus intranasally and intratracheally. DPV, days postvaccination; DPS, days post–SARS-CoV-2. (B) Replicating viral load (VL) in BAL post–SARS-CoV-2 viral challenge. Bar plots denote mean and error bars are SD. Red, blue, and green represent BCG, ALVAC/alum, and control, respectively. Statistical differences between groups for each time point were calculated by the Mann-Whitney/Wilcoxon test, and raw P values < 0.1 are displayed in black. Statistical differences between time points for each group separately were calculated by fitting generalized estimating equations with animal as a random effect, and raw P values < 0.1 are displayed in the color for the group tested. P values above 0.1 were omitted from the figure for clarity and can be found with multiple comparisons adjustments in Supplemental Figure 1F. sgRNA, subgenomic RNA.