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.
Pubmed ID: 19029902 RIS Download
Mesh terms: Adolescent | Adult | Antibodies, Viral | CD8-Positive T-Lymphocytes | Carrier Proteins | Cells, Cultured | Controlled Clinical Trials as Topic | Gene Expression Profiling | Humans | Immunity, Active | Immunity, Innate | Middle Aged | Mitochondrial Proteins | Multivariate Analysis | Neutralization Tests | Protein-Serine-Threonine Kinases | Systems Biology | Tumor Necrosis Factor-alpha | Vaccination | Yellow Fever | Yellow Fever Vaccine | Yellow fever virus | Young Adult
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