Immunomodulatory Effect of the Bacillus Calmette–Guérin (BCG) Vaccine on the <i>In Vitro</i> Interferon Response Induced by Respiratory Syncytial Virus (RSV) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Antigens

Studies on the bacillus Calmette-Guérin (BCG) vaccine, traditionally used against tuberculosis, indicate its potential benefit in protecting against infections. The vaccine's ability to broadly activate the immune system suggests its potential to bolster non-specific immunity, which could be crucial for combating respiratory pathogens. This study aimed to evaluate the messenger RNA (mRNA) expression of interferon (IFN)-α, IFN-β, and IFN-γ as well as the secretion of these cytokines in whole blood co-stimulated cultures with BCG and antigens of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or respiratory syncytial virus (RSV) from BCG-vaccinated Polish children who have been infected or uninfected with RSV and/or SARS-CoV-2. Significant differences were observed in the secretion and mRNA expression of IFN-α and IFN-γ in response to RSV antigens in all groups of children studied. When cultures were conducted in the presence of SARS-CoV-2 antigens, live BCG did not induce increased IFN-α secretion compared with cultures stimulated with these antigens alone. However, enhanced secretion was observed for IFN-γ, and no such relationship was observed for mRNA expression. Furthermore, discrepancies between IFN-β secretion and mRNA expression were observed, suggesting that IFN protein secretion can also be controlled at the translational or posttranslational level. The data from our studies indicate that BCG vaccination may modulate the IFN response to viral challenges with SARS-CoV-2 and RSV, suggesting a potential immunoregulatory role.