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.
Publication types
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Evaluation Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adolescent
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Adult
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Antibodies, Viral / blood
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CD8-Positive T-Lymphocytes / immunology
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Carrier Proteins / genetics
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Cells, Cultured
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Controlled Clinical Trials as Topic
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Gene Expression Profiling / methods*
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Humans
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Immunity, Active / genetics
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Immunity, Innate / genetics*
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Middle Aged
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Mitochondrial Proteins / genetics
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Multivariate Analysis
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Neutralization Tests
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Protein Serine-Threonine Kinases / genetics
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Systems Biology / methods*
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Tumor Necrosis Factor-alpha / genetics
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Vaccination
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Yellow Fever / prevention & control*
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Yellow Fever Vaccine / immunology*
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Yellow Fever Vaccine / therapeutic use
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Yellow fever virus / immunology*
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Young Adult
Substances
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Antibodies, Viral
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C1QBP protein, human
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Carrier Proteins
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Mitochondrial Proteins
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TNF protein, human
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Tumor Necrosis Factor-alpha
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Yellow Fever Vaccine
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EIF2AK4 protein, human
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Protein Serine-Threonine Kinases