Trained immunity: consequences for the heterologous effects of BCG vaccination

A growing body of evidence from epidemiologic and immunologic studies have shown that in addition to target disease-specific effects, vaccines have heterologous effects towards unrelated pathogens. Like some other vaccines, bacille Calmette-Guerin (BCG) has shown in observational studies and randomized clinical trials to increase survival beyond the disease burden of the target disease. The immunologic substrate for these non-specific protective effects have been ascertained to heterologous T cell effects on the one hand, and to priming of innate immunity on the other hand. The term 'trained immunity' has been proposed to describe these potentiating effects of vaccines on innate immune responses. This process can explain the rapid effects of BCG vaccination and has been suggested to be mediated by epigenetic programming of monocytes or macrophages. This novel concept has important implications for the possible use of vaccines, for vaccination policy and even for the design of novel immunotherapeutic approaches.