newborn baby
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The Bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) can protect newborn babies against infections other than TB through changes to lipids and metabolites related to the immune system, shows research led by Harvard Medical School.

The BCG vaccination has been available for 100 years and while its efficacy at preventing infection varies in adults, it is thought to have 60-80% efficacy at protecting against severe TB in children.

In countries where TB is endemic the BCG vaccination is recommended for newborn babies to protect them against miliary TB and tuberculous meningitis. In these areas, research suggests that children given this early vaccination also appear to be resistant to other non-TB infections and have significantly reduced sickness and mortality over what might be expected from TB vaccination alone.

Joann Diray-Arce, a researcher based at Boston Children’s Hospital and Harvard Medical School, and colleagues carried out a study to try and assess why the BCG vaccination might give infants additional protection against other infections.

As described in Cell Reports, the team investigated metabolic and lipid changes that could impact this response in blood samples taken from vaccinated newborns from the Gambia. They were compared with samples from children vaccinated at 6 weeks of age.

Metabolomic and lipidomic analysis revealed changes in the blood plasma in the newborn group that were distinct from children given later vaccination. These changes appear to be linked with the production of immune cytokines, an important part of the immune response to infection. The team showed a link with lysophosphatidylcholine production in the plasma that appeared to be triggered by BCG vaccination and appeared to stimulate immune cell production.

“We now have some lipid and metabolic biomarkers of vaccine protection that we can test and manipulate in mouse models,” said Diray-Arce, in a press statement. “We studied three different BCG formulations and showed that they converge on similar pathways of interest. Reshaping of the metabolome by BCG may contribute to the molecular mechanisms of a newborn’s immune response.”

The team wants to increase its knowledge of how this apparent immune boost works and assess if the process could be used to help more children.

“It’s critical that we learn from BCG to better understand how to protect newborns,” commented Ofer Levy, director of the Precision Vaccines Program and the study’s senior investigator.

“BCG is an ‘old school’ vaccine—it’s made from a live, weakened germ—but live vaccines like BCG seem to activate the immune system in a very different way in early life, providing broad protection against a range of bacterial and viral infections. There’s much work ahead to better understand that and use that information to build better vaccines for infants.”

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