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

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

^*Corresponding author for this work

Department of Health Technology

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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.

Original language	English
Article number	110772
Journal	Cell Reports
Volume	39
Issue number	5
Number of pages	24
ISSN	2211-1247
DOIs	https://doi.org/10.1016/j.celrep.2022.110772
Publication status	Published - 2022

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Diray-Arce, J., Angelidou, A., Jensen, K. J., Conti, M. G., Kelly, R. S., Pettengill, M. A., Liu, M., van Haren, S. D., McCulloch, S. D., Michelloti, G., Idoko, O., EPIC Consortium, Kollmann, T. R., Kampmann, B., Steen, H., Ozonoff, A., Lasky-Su, J., Benn, C. S., & Levy, O. (2022). Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro. Cell Reports, 39(5), Article 110772. https://doi.org/10.1016/j.celrep.2022.110772

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title = "Bacille Calmette-Gu{\'e}rin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro",

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-Gu{\'e}rin (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.",

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

note = "Publisher Copyright: {\textcopyright} 2022 The Authors",

year = "2022",

doi = "10.1016/j.celrep.2022.110772",

language = "English",

volume = "39",

journal = "Cell Reports",

issn = "2211-1247",

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Diray-Arce, J, Angelidou, A, Jensen, KJ, Conti, MG, Kelly, RS, Pettengill, MA, Liu, M, van Haren, SD, McCulloch, SD, Michelloti, G, Idoko, O, EPIC Consortium, Kollmann, TR, Kampmann, B, Steen, H, Ozonoff, A, Lasky-Su, J, Benn, CS & Levy, O 2022, 'Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro', Cell Reports, vol. 39, no. 5, 110772. https://doi.org/10.1016/j.celrep.2022.110772

TY - JOUR

T1 - Bacille Calmette-Guérin vaccine reprograms human neonatal lipid metabolism in vivo and in vitro

AU - Diray-Arce, Joann

AU - Angelidou, Asimenia

AU - Jensen, Kristoffer Jarlov

AU - Conti, Maria Giulia

AU - Kelly, Rachel S.

AU - Pettengill, Matthew A.

AU - Liu, Mark

AU - van Haren, Simon D.

AU - McCulloch, Scott D.

AU - Michelloti, Greg

AU - Idoko, Olubukola

AU - EPIC Consortium

AU - Kollmann, Tobias R.

AU - Kampmann, Beate

AU - Steen, Hanno

AU - Ozonoff, Al

AU - Lasky-Su, Jessica

AU - Benn, Christine S.

AU - Levy, Ofer

PY - 2022

Y1 - 2022

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2022.110772

DO - 10.1016/j.celrep.2022.110772

M3 - Journal article

C2 - 35508141

AN - SCOPUS:85129428939

SN - 2211-1247

VL - 39

JO - Cell Reports

JF - Cell Reports

IS - 5

M1 - 110772

ER -

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

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