Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans.
Nat Immunol, 2009/1;10(1):116-125.
Querec TD[1], Akondy RS[1], Lee EK[2], Cao W[1], Nakaya HI[1], Teuwen D[3], Pirani A[4], Gernert K[4], Deng J[1], Marzolf B[5], Kennedy K[5], Wu H[5], Bennouna S[1], Oluoch H[1], Miller J[1], Vencio RZ[5], Mulligan M[1, 6], Aderem A[5], Ahmed R[1], Pulendran B[1, 7]
Affiliations
PMID: 19029902DOI: 10.1038/ni.1688
Impact factor: 31.25
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.
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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