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,
Tobias R. Kollmann,
Beate Kampmann,
Hanno Steen,
Al Ozonoff,
Jessica Lasky-Su,
Christine S. Benn,
Ofer Levy
Affiliations
Joann Diray-Arce
Precision Vaccines Program, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Corresponding author
Asimenia Angelidou
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
Kristoffer Jarlov Jensen
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
Maria Giulia Conti
Precision Vaccines Program, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Maternal and Child Health, Sapienza University of Rome, 00185 Rome, Italy
Rachel S. Kelly
Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Matthew A. Pettengill
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
Mark Liu
Precision Vaccines Program, Boston Children’s Hospital, Boston, MA 02115, USA
Simon D. van Haren
Precision Vaccines Program, Boston Children’s Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
Scott D. McCulloch
Metabolon, Morrisville, NC 27560, USA
Greg Michelloti
Metabolon, Morrisville, NC 27560, USA
Olubukola Idoko
The Vaccine Centre, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
Tobias R. Kollmann
Telethon Kids Institute, University of Western Australia, Perth, WA 6009, Australia
Beate Kampmann
The Vaccine Centre, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK
Hanno Steen
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
Al Ozonoff
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
Jessica Lasky-Su
Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA
Christine S. Benn
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
Ofer Levy
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
Summary: 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.
