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Nat Immunol. 2009 Jan;10(1):116-125. doi: 10.1038/ni.1688. Epub 2008 Nov 23.

Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.

Author information

1
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
2
Center for Operations Research in Medicine & Healthcare, School of Industrial & Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
3
Sanofi Pasteur, 2 avenue Pont Pasteur, Lyon Cedex 07, France.
4
BimCore, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
5
Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
6
The Hope Clinic, 603 Church Street, Decatur, Georgia 30030, USA.
7
Department of Pathology & Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, USA.
#
Contributed equally

Abstract

A major challenge in vaccinology is to prospectively determine vaccine efficacy. Here we have used a systems biology approach to identify early gene 'signatures' that predicted immune responses in humans vaccinated with yellow fever vaccine YF-17D. Vaccination induced genes that regulate virus innate sensing and type I interferon production. Computational analyses identified a gene signature, including complement protein C1qB and eukaryotic translation initiation factor 2 alpha kinase 4-an orchestrator of the integrated stress response-that correlated with and predicted YF-17D CD8(+) T cell responses with up to 90% accuracy in an independent, blinded trial. A distinct signature, including B cell growth factor TNFRS17, predicted the neutralizing antibody response with up to 100% accuracy. These data highlight the utility of systems biology approaches in predicting vaccine efficacy.

Comment in

PMID:
19029902
PMCID:
PMC4049462
DOI:
10.1038/ni.1688
[Indexed for MEDLINE]
Free PMC Article

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