title: Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
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.
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Troy D
authors.initials: TD
authors.lastname: Querec
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Rama S
authors.initials: RS
authors.lastname: Akondy
authors.affiliation: Center for Operations Research in Medicine & Healthcare, School of Industrial & Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
authors.forename: Eva K
authors.initials: EK
authors.lastname: Lee
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Cao
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Helder I
authors.initials: HI
authors.lastname: Nakaya
authors.affiliation: Sanofi Pasteur, 2 avenue Pont Pasteur, Lyon Cedex 07, France.
authors.forename: Dirk
authors.initials: D
authors.lastname: Teuwen
authors.affiliation: BimCore, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Pirani
authors.affiliation: BimCore, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
authors.forename: Kim
authors.initials: K
authors.lastname: Gernert
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Jiusheng
authors.initials: J
authors.lastname: Deng
authors.affiliation: Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
authors.forename: Bruz
authors.initials: B
authors.lastname: Marzolf
authors.affiliation: Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Kennedy
authors.affiliation: Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wu
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Soumaya
authors.initials: S
authors.lastname: Bennouna
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Herold
authors.initials: H
authors.lastname: Oluoch
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Miller
authors.affiliation: Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
authors.forename: Ricardo Z
authors.initials: RZ
authors.lastname: Vencio
authors.affiliation: 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.
authors.forename: Mark
authors.initials: M
authors.lastname: Mulligan
authors.affiliation: Institute for Systems Biology, 1441 North 34 Street, Seattle, Washington 98103-8904, USA.
authors.forename: Alan
authors.initials: A
authors.lastname: Aderem
authors.affiliation: Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
authors.forename: Rafi
authors.initials: R
authors.lastname: Ahmed
authors.affiliation: 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.
authors.forename: Bali
authors.initials: B
authors.lastname: Pulendran
mesh_terms: D000293:Adolescent; D000328:Adult; D000914:Antibodies, Viral / Q000097:blood; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D018849:Controlled Clinical Trials as Topic; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D007110:Immunity, Active / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics*; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics; D015999:Multivariate Analysis; D009500:Neutralization Tests; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D049490:Systems Biology / Q000379:methods*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D014611:Vaccination; D015004:Yellow Fever / Q000517:prevention & control*; D022341:Yellow Fever Vaccine / Q000276:immunology* / Q000627:therapeutic use; D015005:Yellow fever virus / Q000276:immunology*; D055815:Young Adult
chemical_list: D000914:Antibodies, Viral; C087299:C1QBP protein, human; D002352:Carrier Proteins; D024101:Mitochondrial Proteins; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D022341:Yellow Fever Vaccine; C529271:EIF2AK4 protein, human; D017346:Protein Serine-Threonine Kinases