In Science Advances, a team from Australia and the Netherlands follows the epigenetic and other effects of the tuberculosis-targeting Bacille Calmette-Guérin (BCG) vaccine in an in vitro trained immunity model and in peripheral blood monocyte samples collected from 130 BCG-vaccinated or unvaccinated infants. With a combination of RNA sequencing, chromatin immunoprecipitation sequencing, array-based methylation profiling, RNA editing, expression quantitative trait locus mapping, and other approaches, the researchers saw viral response-related interferon (IFN)-related response to BCG vaccination, along with circulating monocyte DNA methylation shifts that persisted over time. "[W]e identify a BCG-associated DNA methylation signature that persisted more than 12 months after neonatal BCG vaccination," the authors report, noting that "[g]enes associated with this epigenetic signature are involved in viral response pathways, consistent with the reported off-target protection against viral infections in neonates, adults, and the elderly."