Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses

Stefan Avey; Foo Cheung; Damian Fermin; Jacob Frelinger; Renaud Gaujoux; Raphael Gottardo; Purvesh Khatri; Steven H. Kleinstein; Yuri Kotliarov; Hailong Meng; Renan Sauteraud; Shai S. Shen-Orr; John S. Tsang; Francesco Vallania; Esperanza Anguiano; Jeanine Baisch; Nicole Baldwin; Robert B. Belshe; Tamara P. Blevins; Damien Chaussabel; Mark M. Davis; Erol Fikrig; Diane E. Grill; David A. Hafler; Evan Henrich; Samit R. Joshi; Susan M. Kaech; Rick B. Kennedy; Subhasis Mohanty; Ruth R. Montgomery; Ann L. Oberg; Gerlinde Obermoser; Inna G. Ovsyannikova; A. Karolina Palucka; Virginia Pascual; Greg A. Poland; Bali Pulendran; Ellis L. Reinherz; Albert C. Shaw; Barbara Siconolfi; Kenneth D. Stuart; Sui Tsang; Ikuyo Ueda; Jean Wilson; Heidi J. Zapata

doi:10.1126/sciimmunol.aal4656

Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses

Stefan Avey, Foo Cheung, Damian Fermin, Jacob Frelinger, Renaud Gaujoux, Raphael Gottardo, Purvesh Khatri, Steven H. Kleinstein, Yuri Kotliarov, Hailong Meng, Renan Sauteraud, Shai S. Shen-Orr, John S. Tsang, Francesco Vallania, Esperanza Anguiano, Jeanine Baisch, Nicole Baldwin, Robert B. Belshe, Tamara P. Blevins, Damien ChaussabelMark M. Davis, Erol Fikrig, Diane E. Grill, David A. Hafler, Evan Henrich, Samit R. Joshi, Susan M. Kaech, Rick B. Kennedy, Subhasis Mohanty, Ruth R. Montgomery, Ann L. Oberg, Gerlinde Obermoser, Inna G. Ovsyannikova, A. Karolina Palucka, Virginia Pascual, Greg A. Poland, Bali Pulendran, Ellis L. Reinherz, Albert C. Shaw, Barbara Siconolfi, Kenneth D. Stuart, Sui Tsang, Ikuyo Ueda, Jean Wilson, Heidi J. Zapata

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Abstract

Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination are an important mechanism of protection against infection. Despite the overall public health success of influenza vaccination, many individuals fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional and cell subset signatures with the success of antibody responses. However, existing signatures have relied on small cohorts and have not been validated in large independent studies. We leveraged multiple influenza vaccination cohorts spanning distinct geographical locations and seasons from the Human Immunology Project Consortium (HIPC) and the Center for Human Immunology (CHI) to identify baseline (i.e., before vaccination) predictive transcriptional signatures of influenza vaccination responses. Our multicohort analysis of HIPC data identified nine genes (RAB24, GRB2, DPP3, ACTB, MVP, DPP7, ARPC4, PLEKHB2, and ARRB1) and three gene modules that were significantly associated with the magnitude of the antibody response, and these associations were validated in the independent CHI cohort. These signatures were specific to young individuals, suggesting that distinct mechanisms underlie the lower vaccine response in older individuals. We found an inverse correlation between the effect size of signatures in young and older individuals. Although the presence of an inflammatory gene signature, for example, was associated with better antibody responses in young individuals, it was associated with worse responses in older individuals. These results point to the prospect of predicting antibody responses before vaccination and provide insights into the biological mechanisms underlying successful vaccination responses.

Original language	English (US)
Article number	eaal4656
Journal	Science Immunology
Volume	2
Issue number	14
DOIs	https://doi.org/10.1126/sciimmunol.aal4656
State	Published - Apr 25 2017

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Avey, S., Cheung, F., Fermin, D., Frelinger, J., Gaujoux, R., Gottardo, R., Khatri, P., Kleinstein, S. H., Kotliarov, Y., Meng, H., Sauteraud, R., Shen-Orr, S. S., Tsang, J. S., Vallania, F., Anguiano, E., Baisch, J., Baldwin, N., Belshe, R. B., Blevins, T. P., ... Zapata, H. J. (2017). Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses. Science Immunology, 2(14), Article eaal4656. https://doi.org/10.1126/sciimmunol.aal4656

Avey, S, Cheung, F, Fermin, D, Frelinger, J, Gaujoux, R, Gottardo, R, Khatri, P, Kleinstein, SH, Kotliarov, Y, Meng, H, Sauteraud, R, Shen-Orr, SS, Tsang, JS, Vallania, F, Anguiano, E, Baisch, J, Baldwin, N, Belshe, RB, Blevins, TP, Chaussabel, D, Davis, MM, Fikrig, E, Grill, DE, Hafler, DA, Henrich, E, Joshi, SR, Kaech, SM, Kennedy, RB, Mohanty, S, Montgomery, RR, Oberg, AL, Obermoser, G, Ovsyannikova, IG, Karolina Palucka, A, Pascual, V, Poland, GA, Pulendran, B, Reinherz, EL, Shaw, AC, Siconolfi, B, Stuart, KD, Tsang, S, Ueda, I, Wilson, J & Zapata, HJ 2017, 'Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses', Science Immunology, vol. 2, no. 14, eaal4656. https://doi.org/10.1126/sciimmunol.aal4656

@article{e659a011fc6b444980e55dc4f05489d0,

title = "Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses",

abstract = "Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination are an important mechanism of protection against infection. Despite the overall public health success of influenza vaccination, many individuals fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional and cell subset signatures with the success of antibody responses. However, existing signatures have relied on small cohorts and have not been validated in large independent studies. We leveraged multiple influenza vaccination cohorts spanning distinct geographical locations and seasons from the Human Immunology Project Consortium (HIPC) and the Center for Human Immunology (CHI) to identify baseline (i.e., before vaccination) predictive transcriptional signatures of influenza vaccination responses. Our multicohort analysis of HIPC data identified nine genes (RAB24, GRB2, DPP3, ACTB, MVP, DPP7, ARPC4, PLEKHB2, and ARRB1) and three gene modules that were significantly associated with the magnitude of the antibody response, and these associations were validated in the independent CHI cohort. These signatures were specific to young individuals, suggesting that distinct mechanisms underlie the lower vaccine response in older individuals. We found an inverse correlation between the effect size of signatures in young and older individuals. Although the presence of an inflammatory gene signature, for example, was associated with better antibody responses in young individuals, it was associated with worse responses in older individuals. These results point to the prospect of predicting antibody responses before vaccination and provide insights into the biological mechanisms underlying successful vaccination responses.",

author = "Stefan Avey and Foo Cheung and Damian Fermin and Jacob Frelinger and Renaud Gaujoux and Raphael Gottardo and Purvesh Khatri and Kleinstein, {Steven H.} and Yuri Kotliarov and Hailong Meng and Renan Sauteraud and Shen-Orr, {Shai S.} and Tsang, {John S.} and Francesco Vallania and Esperanza Anguiano and Jeanine Baisch and Nicole Baldwin and Belshe, {Robert B.} and Blevins, {Tamara P.} and Damien Chaussabel and Davis, {Mark M.} and Erol Fikrig and Grill, {Diane E.} and Hafler, {David A.} and Evan Henrich and Joshi, {Samit R.} and Kaech, {Susan M.} and Kennedy, {Rick B.} and Subhasis Mohanty and Montgomery, {Ruth R.} and Oberg, {Ann L.} and Gerlinde Obermoser and Ovsyannikova, {Inna G.} and {Karolina Palucka}, A. and Virginia Pascual and Poland, {Greg A.} and Bali Pulendran and Reinherz, {Ellis L.} and Shaw, {Albert C.} and Barbara Siconolfi and Stuart, {Kenneth D.} and Sui Tsang and Ikuyo Ueda and Jean Wilson and Zapata, {Heidi J.}",

note = "Publisher Copyright: Copyright {\textcopyright} 2017 The Author.",

year = "2017",

month = apr,

day = "25",

doi = "10.1126/sciimmunol.aal4656",

language = "English (US)",

volume = "2",

journal = "Science Immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

number = "14",

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TY - JOUR

T1 - Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses

AU - Avey, Stefan

AU - Cheung, Foo

AU - Fermin, Damian

AU - Frelinger, Jacob

AU - Gaujoux, Renaud

AU - Gottardo, Raphael

AU - Khatri, Purvesh

AU - Kleinstein, Steven H.

AU - Kotliarov, Yuri

AU - Meng, Hailong

AU - Sauteraud, Renan

AU - Shen-Orr, Shai S.

AU - Tsang, John S.

AU - Vallania, Francesco

AU - Anguiano, Esperanza

AU - Baisch, Jeanine

AU - Baldwin, Nicole

AU - Belshe, Robert B.

AU - Blevins, Tamara P.

AU - Chaussabel, Damien

AU - Davis, Mark M.

AU - Fikrig, Erol

AU - Grill, Diane E.

AU - Hafler, David A.

AU - Henrich, Evan

AU - Joshi, Samit R.

AU - Kaech, Susan M.

AU - Kennedy, Rick B.

AU - Mohanty, Subhasis

AU - Montgomery, Ruth R.

AU - Oberg, Ann L.

AU - Obermoser, Gerlinde

AU - Ovsyannikova, Inna G.

AU - Karolina Palucka, A.

AU - Pascual, Virginia

AU - Poland, Greg A.

AU - Pulendran, Bali

AU - Reinherz, Ellis L.

AU - Shaw, Albert C.

AU - Siconolfi, Barbara

AU - Stuart, Kenneth D.

AU - Tsang, Sui

AU - Ueda, Ikuyo

AU - Wilson, Jean

AU - Zapata, Heidi J.

PY - 2017/4/25

Y1 - 2017/4/25

N2 - Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination are an important mechanism of protection against infection. Despite the overall public health success of influenza vaccination, many individuals fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional and cell subset signatures with the success of antibody responses. However, existing signatures have relied on small cohorts and have not been validated in large independent studies. We leveraged multiple influenza vaccination cohorts spanning distinct geographical locations and seasons from the Human Immunology Project Consortium (HIPC) and the Center for Human Immunology (CHI) to identify baseline (i.e., before vaccination) predictive transcriptional signatures of influenza vaccination responses. Our multicohort analysis of HIPC data identified nine genes (RAB24, GRB2, DPP3, ACTB, MVP, DPP7, ARPC4, PLEKHB2, and ARRB1) and three gene modules that were significantly associated with the magnitude of the antibody response, and these associations were validated in the independent CHI cohort. These signatures were specific to young individuals, suggesting that distinct mechanisms underlie the lower vaccine response in older individuals. We found an inverse correlation between the effect size of signatures in young and older individuals. Although the presence of an inflammatory gene signature, for example, was associated with better antibody responses in young individuals, it was associated with worse responses in older individuals. These results point to the prospect of predicting antibody responses before vaccination and provide insights into the biological mechanisms underlying successful vaccination responses.

AB - Annual influenza vaccinations are currently recommended for all individuals 6 months and older. Antibodies induced by vaccination are an important mechanism of protection against infection. Despite the overall public health success of influenza vaccination, many individuals fail to induce a substantial antibody response. Systems-level immune profiling studies have discerned associations between transcriptional and cell subset signatures with the success of antibody responses. However, existing signatures have relied on small cohorts and have not been validated in large independent studies. We leveraged multiple influenza vaccination cohorts spanning distinct geographical locations and seasons from the Human Immunology Project Consortium (HIPC) and the Center for Human Immunology (CHI) to identify baseline (i.e., before vaccination) predictive transcriptional signatures of influenza vaccination responses. Our multicohort analysis of HIPC data identified nine genes (RAB24, GRB2, DPP3, ACTB, MVP, DPP7, ARPC4, PLEKHB2, and ARRB1) and three gene modules that were significantly associated with the magnitude of the antibody response, and these associations were validated in the independent CHI cohort. These signatures were specific to young individuals, suggesting that distinct mechanisms underlie the lower vaccine response in older individuals. We found an inverse correlation between the effect size of signatures in young and older individuals. Although the presence of an inflammatory gene signature, for example, was associated with better antibody responses in young individuals, it was associated with worse responses in older individuals. These results point to the prospect of predicting antibody responses before vaccination and provide insights into the biological mechanisms underlying successful vaccination responses.

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U2 - 10.1126/sciimmunol.aal4656

DO - 10.1126/sciimmunol.aal4656

M3 - Article

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SN - 2470-9468

VL - 2

JO - Science Immunology

JF - Science Immunology

IS - 14

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ER -

Multicohort analysis reveals baseline transcriptional predictors of influenza vaccination responses

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