Unleashing the power of the BCG vaccine in modulating viral immunity through heterologous protection: A scoping review.

The Bacillus Calmette-Guérin (BCG) vaccine, used against tuberculosis for a century, shows promise in protecting against viral infections through trained/innate immunity. This review maps clinical and preclinical studies on both parental (WT) and recombinant BCG (rBCG) against 17 common viruses. From 68 studies, BCG strains were found to enhance innate immune responses by reprogramming myeloid cells, leading to stronger responses to related infections. Sixteen rBCG candidates expressed viral antigens, activating CD4+ and CD8+ T cells, and stimulating antibody production specific to the viral antigens. However, challenges like genetic stability and varied efficacy among BCG strains remain. The review highlights the potential of BCG, especially rBCG, as a multivalent vaccine platform for immunization campaigns, with significant public health implications. More translational studies and clinical trials are needed to confirm these findings.