Resources abstract
Nature Immunology 10, 116 - 125 (2008)
Published online: 23 November 2008 | doi:10.1038/ni.1688
Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans
Troy D Querec1,8, Rama S Akondy1,8, Eva K Lee2, Weiping Cao1, Helder I Nakaya1, Dirk Teuwen3, Ali Pirani4, Kim Gernert4, Jiusheng Deng1, Bruz Marzolf5, Kathleen Kennedy5, Haiyan Wu5, Soumaya Bennouna1, Herold Oluoch1, Joseph Miller1, Ricardo Z Vencio5, Mark Mulligan1,6, Alan Aderem5, Rafi Ahmed1 & Bali Pulendran1,7
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.
- Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia 30329, USA.
- Center for Operations Research in Medicine & Healthcare, School of Industrial & Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia 30332, USA.
- Sanofi Pasteur, 2 avenue Pont Pasteur, Lyon Cedex 07, France.
- BimCore, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia 30322, USA.
- Institute for Systems Biology, 1441 North 34th Street, Seattle, Washington 98103-8904, USA.
- The Hope Clinic, 603 Church Street, Decatur, Georgia 30030, USA.
- Department of Pathology & Laboratory Medicine, Emory University, 1364 Clifton Road, Atlanta, Georgia 30322, USA.
- These authors contributed equally to this work.
Correspondence to: Bali Pulendran1,7 e-mail: bpulend@rmy.emory.edu
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