Metabolic Phenotypes of Response to Vaccination in Humans

Shuzhao Li; Nicole L. Sullivan; Nadine Rouphael; Tianwei Yu; Sophia Banton; Mohan S. Maddur; Megan McCausland; Christopher Chiu; Jennifer Canniff; Sheri Dubey; Ken Liu; Vi Linh Tran; Thomas Hagan; Sai Duraisingham; Andreas Wieland; Aneesh K. Mehta; Jennifer A. Whitaker; Shankar Subramaniam; Dean P. Jones; Alessandro Sette; Kalpit Vora; Adriana Weinberg; Mark J. Mulligan; Helder I. Nakaya; Myron Levin; Rafi Ahmed; Bali Pulendran

doi:10.1016/j.cell.2017.04.026

Metabolic Phenotypes of Response to Vaccination in Humans

Shuzhao Li, Nicole L. Sullivan, Nadine Rouphael, Tianwei Yu, Sophia Banton, Mohan S. Maddur, Megan McCausland, Christopher Chiu, Jennifer Canniff, Sheri Dubey, Ken Liu, Vi Linh Tran, Thomas Hagan, Sai Duraisingham, Andreas Wieland, Aneesh K. Mehta, Jennifer A. Whitaker, Shankar Subramaniam, Dean P. Jones, Alessandro SetteKalpit Vora, Adriana Weinberg, Mark J. Mulligan, Helder I. Nakaya, Myron Levin, Rafi Ahmed, Bali Pulendran

General Internal Medicine

Research output: Contribution to journal › Article › peer-review

111 Scopus citations

Abstract

Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4⁺ T cells yet limited CD8⁺ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.

Original language	English (US)
Pages (from-to)	862-877.e17
Journal	Cell
Volume	169
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2017.04.026
State	Published - May 18 2017

Keywords

Zostavax
herpes zoster vaccine
immune response
metabolomics
multiscale
shingles
systems biology
transcriptomics

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

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10.1016/j.cell.2017.04.026

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Li, S., Sullivan, N. L., Rouphael, N., Yu, T., Banton, S., Maddur, M. S., McCausland, M., Chiu, C., Canniff, J., Dubey, S., Liu, K., Tran, V. L., Hagan, T., Duraisingham, S., Wieland, A., Mehta, A. K., Whitaker, J. A., Subramaniam, S., Jones, D. P., ... Pulendran, B. (2017). Metabolic Phenotypes of Response to Vaccination in Humans. Cell, 169(5), 862-877.e17. https://doi.org/10.1016/j.cell.2017.04.026

Li, S, Sullivan, NL, Rouphael, N, Yu, T, Banton, S, Maddur, MS, McCausland, M, Chiu, C, Canniff, J, Dubey, S, Liu, K, Tran, VL, Hagan, T, Duraisingham, S, Wieland, A, Mehta, AK, Whitaker, JA, Subramaniam, S, Jones, DP, Sette, A, Vora, K, Weinberg, A, Mulligan, MJ, Nakaya, HI, Levin, M, Ahmed, R & Pulendran, B 2017, 'Metabolic Phenotypes of Response to Vaccination in Humans', Cell, vol. 169, no. 5, pp. 862-877.e17. https://doi.org/10.1016/j.cell.2017.04.026

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title = "Metabolic Phenotypes of Response to Vaccination in Humans",

abstract = "Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.",

keywords = "Zostavax, herpes zoster vaccine, immune response, metabolomics, multiscale, shingles, systems biology, transcriptomics",

author = "Shuzhao Li and Sullivan, {Nicole L.} and Nadine Rouphael and Tianwei Yu and Sophia Banton and Maddur, {Mohan S.} and Megan McCausland and Christopher Chiu and Jennifer Canniff and Sheri Dubey and Ken Liu and Tran, {Vi Linh} and Thomas Hagan and Sai Duraisingham and Andreas Wieland and Mehta, {Aneesh K.} and Whitaker, {Jennifer A.} and Shankar Subramaniam and Jones, {Dean P.} and Alessandro Sette and Kalpit Vora and Adriana Weinberg and Mulligan, {Mark J.} and Nakaya, {Helder I.} and Myron Levin and Rafi Ahmed and Bali Pulendran",

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year = "2017",

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doi = "10.1016/j.cell.2017.04.026",

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AU - Sullivan, Nicole L.

AU - Rouphael, Nadine

AU - Yu, Tianwei

AU - Banton, Sophia

AU - Maddur, Mohan S.

AU - McCausland, Megan

AU - Chiu, Christopher

AU - Canniff, Jennifer

AU - Dubey, Sheri

AU - Liu, Ken

AU - Tran, Vi Linh

AU - Hagan, Thomas

AU - Duraisingham, Sai

AU - Wieland, Andreas

AU - Mehta, Aneesh K.

AU - Whitaker, Jennifer A.

AU - Subramaniam, Shankar

AU - Jones, Dean P.

AU - Sette, Alessandro

AU - Vora, Kalpit

AU - Weinberg, Adriana

AU - Mulligan, Mark J.

AU - Nakaya, Helder I.

AU - Levin, Myron

AU - Ahmed, Rafi

AU - Pulendran, Bali

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AB - Herpes zoster (shingles) causes significant morbidity in immune compromised hosts and older adults. Whereas a vaccine is available for prevention of shingles, its efficacy declines with age. To help to understand the mechanisms driving vaccinal responses, we constructed a multiscale, multifactorial response network (MMRN) of immunity in healthy young and older adults immunized with the live attenuated shingles vaccine Zostavax. Vaccination induces robust antigen-specific antibody, plasmablasts, and CD4+ T cells yet limited CD8+ T cell and antiviral responses. The MMRN reveals striking associations between orthogonal datasets, such as transcriptomic and metabolomics signatures, cell populations, and cytokine levels, and identifies immune and metabolic correlates of vaccine immunity. Networks associated with inositol phosphate, glycerophospholipids, and sterol metabolism are tightly coupled with immunity. Critically, the sterol regulatory binding protein 1 and its targets are key integrators of antibody and T follicular cell responses. Our approach is broadly applicable to study human immunity and can help to identify predictors of efficacy as well as mechanisms controlling immunity to vaccination.

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JO - Cell

JF - Cell

IS - 5

ER -

Metabolic Phenotypes of Response to Vaccination in Humans

Abstract

Keywords

ASJC Scopus subject areas

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