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Author Notes:

Correspondence: shankar@ucsd.edu (S.S.), bpulend@emory.edu (B.P.).

H.I.N., S.S.D., M.K., N.R., D.F., A.K.M., G.-M.L., R.A., M.J.M., and B.B.B. collected, processed, and prepared samples and assisted with the analyses.

H.I.N. and T.H. performed most of the microarray analyses.

E.K.L. performed the DAMIP model analyses.

T.H. performed the neural network predictive analyses.

S.S.D. and M.K. performed the FACS analyses.

R.G. and S.S.-O. performed the deconvolution analyses.

S.S. and B.P. supervised the analyses.

M.G. and S.G. assisted with analysis of microarray data.

B.P., R.A., N.R., and M.J.M. conceived the study and designed the experiments.

H.I.N., T.H., S.S., and B.P. wrote the paper.

We are grateful to Mary Bower, Srilatha Edugupanti, and the Hope Clinic Staff who assisted with the clinical work. We also thank Emory Immunology/Flow Cytometry Core for technical assistance.

The GEO accession numbers for the microarray data reported in this paper are GSE74817 (influenza seasons 2009–2012) and GSE29619 (influenza seasons 2007–2009).

Subjects:

Research Funding:

This work was supported by NIH grants U19AI090023 (B.P.), U19AI057266 (R.A. and B.P.), HHSN272201400004C (B.P.), U54AI057157 (B.P.), R37AI48638 (B.P.), and R37DK057665 (B.P.) and NSF Grant STC-0939370 (S.S.).

H.I.N. receives a CNPq (Brazilian Research Council) research fellowship.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • T-CELL RESPONSES
  • SEASONAL INFLUENZA
  • ANTIBODY-RESPONSES
  • DENDRITIC CELLS
  • ACTIVATION
  • HUMANS
  • MICRORNAS

Systems Analysis of Immunity to Influenza Vaccination across Multiple Years and in Diverse Populations Reveals Shared Molecular Signatures

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Journal Title:

Immunity

Volume:

Volume 43, Number 6

Publisher:

, Pages 1186-1198

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Systems approaches have been used to describe molecular signatures driving immunity to influenza vaccination in humans. Whether such signatures are similar across multiple seasons and in diverse populations is unknown. We applied systems approaches to study immune responses in young, elderly, and diabetic subjects vaccinated with the seasonal influenza vaccine across five consecutive seasons. Signatures of innate immunity and plasmablasts correlated with and predicted influenza antibody titers at 1 month after vaccination with >80% accuracy across multiple seasons but were not associated with the longevity of the response. Baseline signatures of lymphocyte and monocyte inflammation were positively and negatively correlated, respectively, with antibody responses at 1 month. Finally, integrative analysis of microRNAs and transcriptomic profiling revealed potential regulators of vaccine immunity. These results identify shared vaccine-induced signatures across multiple seasons and in diverse populations and might help guide the development of next-generation vaccines that provide persistent immunity against influenza.

Copyright information:

© 2015 Elsevier Inc.

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