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

  • Querec, Troy D1
  • Akondy, Rama S1
  • Lee, Eva K2
  • Cao, Weiping1
  • Nakaya, Helder I1
  • Teuwen, Dirk3
  • Pirani, Ali4
  • Gernert, Kim4
  • Deng, Jiusheng1
  • Marzolf, Bruz5
  • Kennedy, Kathleen5
  • Wu, Haiyan5
  • Bennouna, Soumaya1
  • Oluoch, Herold1
  • Miller, Joseph1
  • Vencio, Ricardo Z5
  • Mulligan, Mark1, 6
  • Aderem, Alan5
  • Ahmed, Rafi1
  • Pulendran, Bali1, 7
  • 1 Emory Vaccine Center, Yerkes National Primate Research Center, 954 Gatewood Road, Atlanta, Georgia, 30329, USA , Atlanta (United States)
  • 2 Center for Operations Research in Medicine & Healthcare, School of Industrial & Systems Engineering, Georgia Institute of Technology, Atlanta, Georgia, 30332, USA , Atlanta (United States)
  • 3 Sanofi Pasteur, 2 avenue Pont Pasteur, Lyon, Cedex 07, France , Lyon (France)
  • 4 BimCore, Emory University School of Medicine, 1510 Clifton Road, Atlanta, Georgia, 30322, USA , Atlanta (United States)
  • 5 Institute for Systems Biology, 1441 North 34th Street, Seattle, Washington, 98103-8904, USA , Seattle (United States)
  • 6 The Hope Clinic, 603 Church Street, Decatur, Georgia, 30030, USA , Decatur (United States)
  • 7 Emory University, 1364 Clifton Road, Atlanta, Georgia, 30322, USA , Atlanta (United States)
Published Article
Nature Immunology
Springer Nature
Publication Date
Nov 23, 2008
DOI: 10.1038/ni.1688
Springer Nature


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.

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