The BCG vaccine's mechanism of action is revealed: Republic of Guinea Bissau

The century-old Bacille Calmette-Guérin (BCG) vaccination against TB immunizes 100 million infants annually. Surprisingly, in places with prevalent TB, it protects neonates and babies against several bacterial and viral diseases unrelated to TB. There's even proof it reduces COVID-19.

Why the BCG vaccine? Why does it protect newborns so much? Little is known. The Precision Vaccines Program at Boston Children's Hospital worked with the Expanded Program on Vaccination Consortium (EPIC), an international team investigating early life immunization, to collect and characterize blood samples from babies inoculated with BCG using a sophisticated "big data" technique.

Cell Reports discovered that the BCG vaccination generates particular changes in metabolites and lipids that correspond with innate immune system responses. The discoveries may help make other vaccinations more effective in susceptible groups, such as infants.

Small kids, a huge deal

First author Joann Diray Arce, Ph.D., and colleagues started with blood samples from low-birthweight neonates in Guinea Bissau participating in a randomized clinical study to receive BCG at birth or six weeks later.

Four-week blood samples were obtained from both groups (after BCG was given to the first group, and before it was given to the second group). Using metabolomics and lipidomics, the scientists evaluated BCG's influence on babies' plasma.

BCG vaccinations administered at birth affected metabolite and lipid profiles in neonates' blood plasma. Alterations in innate immunity cytokine production are linked with the changes. Researchers found similar results when testing BCG in cord blood samples from Boston neonates and newborns in The Gambia and Papua New Guinea.

Now we can examine and alter lipid and metabolic vaccination biomarkers in mouse models. We tested three BCG formulations and found comparable routes. Reshaping the metabolome by BCG may contribute to a newborn's immunological response.

" Joann Diray Arce, Boston Children's Hospital

More researches demonstrates that BCG vaccination protects against unrelated illnesses, says Ofer Levy, MD, Ph.D., the study's principal investigator.

We must learn from BCG to safeguard infants. BCG is generated from a live, weakened germ, but live vaccinations appear to impact the immune system differently in early life, offering wide protection against bacterial and viral diseases. To better understand this and produce better newborn immunizations, more effort remains.