Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro

Vaccines have generally been developed with limited insight into their molecular impact. While systems vaccinology enables characterization of mechanisms of action, these tools have yet to be applied to infants, who are at high risk of infection and receive the most vaccines. Bacille Calmette-Guérin (BCG) protects infants against disseminated tuberculosis (TB) and TB-unrelated infections via incompletely understood mechanisms. We employ mass-spectrometry-based metabolomics of blood plasma to profile BCG-induced infant responses in Guinea-Bissau in vivo and the US in vitro. BCG-induced lysophosphatidylcholines (LPCs) correlate with both TLR-agonist- and purified protein derivative (PPD, mycobacterial antigen)-induced blood cytokine production in vitro, raising the possibility that LPCs contribute to BCG immunogenicity. Analysis of an independent newborn cohort from The Gambia demonstrates shared vaccine-induced metabolites, such as phospholipids and sphingolipids. BCG-induced changes to the plasma lipidome and LPCs may contribute to its immunogenicity and inform the development of early life vaccines. [Display omitted] •Neonatal BCG immunization generates distinct metabolic shifts in vivo and in vitro•BCG induces prominent changes in concentrations of plasma lysophospholipids (LPLs)•BCG induces effects on lysophosphatidylcholines correlated with cytokine responses•The impact of vaccine on the metabolome may define signatures of vaccine responses Diray-Arce et al. report that BCG vaccination shifts the plasma metabolome early in life in vivo and in vitro. They also demonstrate that BCG changes in plasma lysophospholipids correlated with TLR-agonist- and mycobacterial-induced cytokine and chemokine responses.