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Author Notes:

Corresponding Author: Bali Pulendran, Ph.D., Emory Vaccine Center, 954 Gatewood Road, Atlanta, GA 30329, USA. Telephone: 404-727-8945. Fax: 404-727-8199. Email: bpulend@emory.edu.

H.I.N. performed all the experiments and analyses in Figures 2–6 and Supplementary Figures 2–10.

J.W., G.M.L., M.M. and V.K. performed the analyses in Figure 1 and Supplementary Figure 1.

E.K.L. performed the DAMIP model analyses in Figure 5.

L.R., A.R.M., S.P.K. and N.K. performed the mouse experiments shown in Figure 6.

W.N.H. helped in microarray experiments shown in Supplementary Figure 5.

S.L. assisted with the bioinformatics analyses of the data in Figure 3.

A.A. performed the microarray experiments of samples from 2007 influenza annual season.

S.M.K., K.E.K., R.E. and A.K.M. assisted with the collection and processing of samples.

K.S. measured the HAI titers.

R.A. helped conceive and design the study and supervised the studies in Figure 1 and Supplementary Figure 1.

B.P. conceived the study and designed and supervised the experiments and analyses in Figures 1–6 and Supplementary Figures 1–10.

B.P. and H.I.N. wrote the paper.

We thank Barry T. Rouse and Richard Compans for discussion and comments on the manuscript.

We thank Herold Oluoch for his excellent technical assistance.

The authors declare no competing financial interests.

Subjects:

Research Funding:

The work in the laboratory of B.P. was supported by grants U19AI090023, HHSN266200700006C, U54AI057157, R37AI48638, R01DK057665, U19AI057266, and NO1 AI50025 from the National Institutes of Health and a grant from the Bill & Melinda Gates Foundation.

Work in R.A. laboratory was partly funded by grants AI30048 (NIH) and AI057266 (NIH), and CAVD 38645 (Bill and Melinda Gates Foundation Grant).

Work in A.R.M. lab was funded by NIH grant DK074701.

Work in K.S. laboratory was supported by the Intramural Research Program of the NIAID, NIH. Work in EKL lab was partially support by NSF and CDC grants.

The clinical work was supported in part by PHS Grant UL1 RR025008 from the Clinical and Translational Science Award program, National Institutes of Health, National Center for Research Resources.

Systems biology of vaccination for seasonal influenza in humans

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Journal Title:

Nature Immunology

Volume:

Volume 12, Number 8

Publisher:

, Pages 786-795

Type of Work:

Article | Post-print: After Peer Review

Abstract:

We used a systems biological approach to study innate and adaptive responses to influenza vaccination in humans, during 3 consecutive influenza seasons. Healthy adults were vaccinated with inactivated (TIV) or live attenuated (LAIV) influenza vaccines. TIV induced greater antibody titers and enhanced numbers of plasmablasts than LAIV. In TIV vaccinees, early molecular signatures correlated with, and accurately predicted, later antibody titers in two independent trials. Interestingly, the expression of Calcium/calmodulin-dependent kinase IV (CamkIV) at day 3 was inversely correlated with later antibody titers. Vaccination of CamkIV −/− mice with TIV induced enhanced antigen-specific antibody titers, demonstrating an unappreciated role for CaMKIV in the regulation of antibody responses. Thus systems approaches can predict immunogenicity, and reveal new mechanistic insights about vaccines.

Copyright information:

© 2011 Nature America, Inc. All rights reserved.

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