Systems Biology Approach Predicts Immunogenicity of the Yellow Fever Vaccine in Humans

Overview

Journal Nat Immunol

Date 2008 Nov 26

PMID 19029902

Citations 637

Authors

Troy D Querec

Rama S Akondy

Eva K Lee

Weiping Cao

Helder I Nakaya

Dirk Teuwen

Ali Pirani

Kim Gernert

Jiusheng Deng

Bruz Marzolf

Kathleen Kennedy

Haiyan Wu

Soumaya Bennouna

Herold Oluoch

Joseph Miller

Ricardo Z Vencio

Mark Mulligan

Alan Aderem

Rafi Ahmed

Bali Pulendran

Affiliations

Soon will be listed here.

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.

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