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

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


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.

Publication types

  • Evaluation Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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*
  • Yellow Fever Vaccine / therapeutic use
  • Yellow fever virus / immunology*
  • Young Adult


  • 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

Associated data

  • GEO/GSE13486