Unravelling the nature of non-specific effects of vaccines-A challenge for innate immunologists

•Vaccines can have non-specific effects on health, beyond their target disease.•Innate immune memory, or ‘trained innate immunity’, can explain some of these effects.•‘Trained innate immunity’ depends on epigenetic reprogramming of innate immune cells.•BCG priming of monocytes in vitro can model ‘trained innate immunity’ invivo.•The biological pathways leading to epigenetic reprogramming need more study.