Induction of Trained Immunity by BCG: Recent Data and Opinions

Bacillus Calmette–Guerin (BCG), developed in the early 20th century to protect against tuberculosis, is one of the most widely used vaccines in the world. In addition to protecting against tuberculosis, this vaccine has also been shown to reduce the risk of various other infections. During the COVID-19 pandemic, it was found that BCG-vaccinated healthcare workers had lower detection rates of the SARS-CoV-2 virus compared to unvaccinated individuals. This appears to be due to the generation of trained immunity (TRIM) and non-specific effects (NSE), which are likely a result of the epigenetic and metabolic reprogramming of innate immune cells, known as trained immunity. NSE further holds promise for the development of future therapeutics that can protect against unpredictable pandemics. Additionally, TRIM inducers provide new perspectives on improving the efficacy of standard vaccines by incorporating them into vaccine formulations to enhance both specific and nonspecific immune responses.