Bacillus Calmette-Guérin-induced trained immunity protects against SARS-CoV-2 challenge in K18-hACE2 mice

JCI Insight. 2022 Jun 8;7(11):e157393. doi: 10.1172/jci.insight.157393.


SARS-CoV-2 has been confirmed in over 450 million confirmed cases since 2019. Although several vaccines have been certified by the WHO and people are being vaccinated on a global scale, it has been reported that multiple SARS-CoV-2 variants can escape neutralization by antibodies, resulting in vaccine breakthrough infections. Bacillus Calmette-Guérin (BCG) is known to induce heterologous protection based on trained immune responses. Here, we investigated whether BCG-induced trained immunity protected against SARS-CoV-2 in the K18-hACE2 mouse model. Our data demonstrate that i.v. BCG (BCG-i.v.) vaccination induces robust trained innate immune responses and provides protection against WT SARS-CoV-2, as well as the B.1.617.1 and B.1.617.2 variants. Further studies suggest that myeloid cell differentiation and activation of the glycolysis pathway are associated with BCG-induced training immunity in K18-hACE2 mice. Overall, our study provides the experimental evidence that establishes a causal relationship between BCG-i.v. vaccination and protection against SARS-CoV-2 challenge.

Keywords: COVID-19; Infectious disease; Innate immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • BCG Vaccine
  • COVID-19* / prevention & control
  • Humans
  • Melphalan
  • Mice
  • SARS-CoV-2*
  • gamma-Globulins


  • BCG Vaccine
  • K-18 conjugate
  • gamma-Globulins
  • Melphalan

Supplementary concepts

  • SARS-CoV-2 variants