An Unlikely Source of Inspiration

The Bacille Calmette-Guérin (BCG) tuberculosis (TB) vaccine is one of the most widely used vaccines globally, but it doesn’t stop there – even at 101 years old, the vaccine may still be a source of inspiration for future vaccine design. It has previously been suggested that BCG’s effects may extend beyond TB to protect infants against other bacterial and viral infections, but the mechanisms remain unclear. Might the answer lie in its origins?

“Unlike many newer vaccines, BCG is made from a live, weakened germ, and may offer unique mechanisms of protection,” said Ofer Levy, director of the Precision Vaccines Program at Boston Children’s Hospital (1). “It’s critical that we learn from BCG so we can better protect newborns, whose immune systems are distinct from those of adults.”

To investigate this, researchers from the Boston Children’s Hospital and the Expanded Program on Immunization Consortium used mass spectrometry-based metabolomics of blood plasma to characterize BCG-induced responses in infants (2). They found that vaccinated infants had distinct metabolic and lipid profiles in their blood compared with unvaccinated infants and that the vaccine’s effects on lysophosphatidylcholines (LPCs) were associated with cytokine responses – suggesting that LPCs may contribute to BCG immunogenicity.

“Old 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,” said Levy (1). The study is one of the first to characterize BCG-induced changes to the human newborn plasma metabolome; previous studies in neonates have used umbilical cord blood for metabolomic profiling.

“We now have some lipid and metabolic biomarkers of vaccine protection that we can test and manipulate in mouse models,” said lead author Joann Diray Arce (1). The next step of the project is to perform that further testing – but there is still much work to be done to fully understand the vaccine’s broad protective effects and apply this to developing better vaccines for infants.

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