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

Joann Diray-Arce, Asimenia Angelidou, Kristoffer Jarlov Jensen, Maria Giulia Conti, Rachel S. Kelly, Matthew A. Pettengill, Mark Liu, Simon D. van Haren, Scott D. McCulloch, Greg Michelloti, Olubukola Idoko, EPIC Consortium, Tobias R. Kollmann, Beate Kampmann, Hanno Steen, Al Ozonoff, Jessica Lasky-Su, Christine S. Benn, Ofer Levy

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Abstrakt

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.

OriginalsprogEngelsk
TidsskriftCell Reports
Vol/bind39
Udgave nummer5
Sider (fra-til)110772
ISSN2211-1247
DOI
StatusUdgivet - 3. maj 2022

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Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.

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