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

doi:10.1016/j.celrep.2022.110772

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

Cell Rep. 2022 May 3;39(5):110772. doi: 10.1016/j.celrep.2022.110772.

Authors

Joann Diray-Arce¹, Asimenia Angelidou², Kristoffer Jarlov Jensen³, Maria Giulia Conti⁴, Rachel S Kelly⁵, Matthew A Pettengill⁶, Mark Liu⁷, Simon D van Haren⁸, Scott D McCulloch⁹, Greg Michelloti⁹, Olubukola Idoko¹⁰; EPIC Consortium; Tobias R Kollmann¹¹, Beate Kampmann¹⁰, Hanno Steen¹², Al Ozonoff¹³, Jessica Lasky-Su⁵, Christine S Benn¹⁴, Ofer Levy¹³

Affiliations

¹ Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA. Electronic address: joann.arce@childrens.harvard.edu.
² Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
³ Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, University of Southern Denmark, 2300 Copenhagen, Denmark; Bandim Health Project, Department of Clinical Research, University of Southern Denmark, 1455 Copenhagen K, Denmark; Experimental and Translational Immunology, Department of Health Technology, Technical University of Denmark, 2800 Kgs, Lyngby, Denmark.
⁴ Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Maternal and Child Health, Sapienza University of Rome, 00185 Rome, Italy.
⁵ Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
⁶ Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA.
⁷ Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA.
⁸ Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA.
⁹ Metabolon, Morrisville, NC 27560, USA.
¹⁰ The Vaccine Centre, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
¹¹ Telethon Kids Institute, University of Western Australia, Perth, WA 6009, Australia.
¹² Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Boston Children's Hospital, Boston, MA 02115, USA.
¹³ Precision Vaccines Program, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Broad Institute of MIT & Harvard, Cambridge, MA 02142, USA.
¹⁴ Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, University of Southern Denmark, 2300 Copenhagen, Denmark; Bandim Health Project, Department of Clinical Research, University of Southern Denmark, 1455 Copenhagen K, Denmark; Danish Institute for Advanced Study, University of Southern Denmark, 5230 Odense M, Denmark.

Abstract

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.

Keywords: BCG; CP: Immunology; innate immunity; lipidomics; lysophosphatidylcholine; metabolism; metabolomics; newborn; systems vaccinology; trained immunity; vaccine.

MeSH terms

Adjuvants, Immunologic
BCG Vaccine*
Humans
Infant
Infant, Newborn
Lipid Metabolism
Tuberculosis*

Substances

Adjuvants, Immunologic
BCG Vaccine

Abstract

MeSH terms

Substances

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