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PMID: 19029902 Published · ppublish English Evaluation Study Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature immunology ·Vol. 10 ·No. 1 ·2009-01-00 ·Pages 116-125

Querec TD, Akondy RS, Lee EK, Cao W, Nakaya HI, Teuwen D, Pirani A, Gernert K, Deng J, Marzolf B, Kennedy K, Wu H, Bennouna S, Oluoch H, Miller J, Vencio RZ, Mulligan M, Aderem A, Ahmed R, Pulendran B

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.

MeSH Terms
Adolescent Adult Antibodies, Viral/blood CD8-Positive T-Lymphocytes/immunology Carrier Proteins/genetics Cells, Cultured Controlled Clinical Trials as Topic Gene Expression Profiling/methods Humans Immunity, Active/genetics Immunity, Innate/genetics Middle Aged Mitochondrial Proteins/genetics Multivariate Analysis Neutralization Tests Protein Serine-Threonine Kinases/genetics Systems Biology/methods Tumor Necrosis Factor-alpha/genetics Vaccination Yellow Fever/prevention & control Yellow Fever Vaccine/immunology,therapeutic use Yellow fever virus/immunology Young Adult
Chemicals
Antibodies, Viral C1QBP protein, human Carrier Proteins Mitochondrial Proteins TNF protein, human Tumor Necrosis Factor-alpha Yellow Fever Vaccine EIF2AK4 protein, human Protein Serine-Threonine Kinases
Authors & Affiliations
20 authors, click to expand affiliations / ORCID
Querec Troy D
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Akondy Rama S
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Lee Eva K
Center for Operations Research in Medicine & Healthcare, School of Industrial & Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
Cao Weiping
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Nakaya Helder I
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Teuwen Dirk
Sanofi Pasteur, 2 avenue Pont Pasteur, Lyon Cedex 07, France.
Pirani Ali
BimCore, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
Gernert Kim
BimCore, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
Deng Jiusheng
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Marzolf Bruz
Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
Kennedy Kathleen
Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
Wu Haiyan
Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
Bennouna Soumaya
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Oluoch Herold
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Miller Joseph
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Vencio Ricardo Z
Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
Mulligan Mark
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. | The Hope Clinic, 603 Church Street, Decatur, Georgia 30030, USA.
Aderem Alan
Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
Ahmed Rafi
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
Pulendran Bali
Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA. | Department of Pathology & Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, USA.
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Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni.1688
Published
2009-01-00
Epub
2008-00-23
Pages
116-125
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC4049462
Subset
IM
Grants
NIAID NIH HHS · R38 AI140299 · United States
NIAID NIH HHS · U19 AI090023 · United States
NIDDK NIH HHS · R01 DK057665 · United States
NIDDK NIH HHS · R37 DK057665 · United States
NCATS NIH HHS · UL1 TR000454 · United States
NIAID NIH HHS · R01 AI048638 · United States
NIAID NIH HHS · U54 AI057157 · United States
NIAID NIH HHS · U19 AI057266 · United States
NIAID NIH HHS · N01 AI050025 · United States
NIAID NIH HHS · N01 AI050019 · United States
NCRR NIH HHS · UL1 RR025008 · United States
Databases
GEO
GSE13486
Corrections
CommentIn
PMID: 19088735
External Links
PubMed source DOI: 10.1038/ni.1688 PMC Full Text View journal details
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