The century-old Bacille Calmette-Guérin (BCG) vaccine against tuberculosis is one of the world’s oldest and most widely used vaccines, used to immunize 100 million newborns every year. Given in countries with endemic TB, this vaccine has surprisingly been found to protect newborns and young infants against multiple bacterial and viral infections unrelated to TB. There’s even some evidence that it can reduce severity of COVID-19. What’s special about BCG vaccine? How does it protect infants so broadly? It turns out little is known. To understand its mechanism of action, researchers at the Precision Vaccines Program at Boston Children’s Hospital partnered with the Expanded Program on Immunization Consortium (EPIC), an international team studying early life immunization, to collect and comprehensively profile blood samples from newborns immunized with BCG, using a powerful “big data” approach. Their study, published online May 3, 2022 in Cell Reports, found that the BCG vaccine induces specific changes in metabolites and lipids that correlate with innate immune system responses. The findings provide clues toward making other vaccines more effective in vulnerable populations with distinct immune systems, such as newborns. The open-access article is titled “Bacille Calmette-Guérin Vaccine Reprograms Human Neonatal Lipid Metabolism in Vivo and in Vitro.”