<p><strong>Bacillus Calmette-Guérin (BCG) is one of the world’s oldest and most widely used vaccines. It was developed in the early 20<sup>th</sup> century to provide protection from tuberculosis. Surprisingly, this vaccine protects not only against tuberculosis but also reduces the risk for various other infections, through a mechanism called trained immunity. A new study led by Christoph Bock and Mihai Netea found that epigenetic cell states predict whether or not an individual profits from the “wake-up call” to the innate immune system that is provided by the BCG vaccine. This discovery contributes to the development of future therapeutics that induce protective trained immunity.</strong></p>