Recombinant BCG Expressing the Subunit 1 of Pertussis Toxin Induces Innate Immune Memory and Confers Protection against Non-Related Pathogens

BCG has shown the ability to induce protection against unrelated pathogens, which likely depends on an immune mechanism known as innate immune memory or trained immunity. In this study, we evaluated the induction of innate memory by a recombinant BCG strain expressing the genetically detoxified S1 subunit of the pertussis toxin (rBCG-S1PT). In vitro pre-exposure of naive murine macrophages to rBCG-S1PT increased their innate/inflammatory response (IL-6, TNF-alpha, and IL-10) to a subsequent challenge with unrelated pathogens, as compared to pre-exposure to wild-type BCG. Following LPS challenge, mice immunized with rBCG-S1PT produced higher levels of IFN-gamma, while the release of other inflammatory cytokines was comparable to that measured after BCG immunization. SCID mice previously immunized with rBCG-S1PT and challenged with pathogenic Candida albicans displayed a similar survival curve as BCG-immunized mice but a lower CFU burden in the kidneys, suggesting an innate memory-dependent control of C. albicans infection. This study highlights the potential of recombinant BCG to increase innate immune memory and, ultimately, non-specific protection, more effectively than wild-type BCG. To our knowledge, this is the first report describing the potential of a recombinant BCG strain to strengthen innate immune memory responses.

Automated summary

This study evaluated the ability of a recombinant BCG strain (rBCG-S1PT) to induce innate immune memory. It was found that pre-exposure of naïve murine macrophages to rBCG-S1PT increased their innate/inflammatory response to unrelated pathogens. Mice immunized with rBCG-S1PT also showed higher levels of IFN-gamma and better control of Candida albicans infection compared to mice immunized with wild-type BCG. These findings suggest the potential of recombinant BCG to enhance innate immune memory and non-specific protection.