Molecular signatures of antibody responses derived from a systems biology study of five human vaccines

• Authors: Shuzhao Li, Emory University; Nadine Rouphael, Emory University; Sai Duraisingham, Emory University; Sandra Romero-Steiner, Centers for Disease Control and Prevention; Scott Presnell, Benaroya Research Institute; Carl Davis, Emory University; Daniel S. Schmidt, Centers for Disease Control and Prevention; Scott E. Johnson, Centers for Disease Control and Prevention; Andrea Milton, Centers for Disease Control and Prevention; Gowrisankar Rajam, Centers for Disease Control and Prevention; Sudhir Kasturi, Emory University; George Carlone, Emory University; Charlie Quinn, Benaroya Research Institute; Damien Chaussabel, Benaroya Research Institute; A. Karolina Palucka, Baylor Research Institute; Mark Mulligan, Emory University; Rafi Ahmed, Emory University; David S Stephens, Emory University; Helder Nakaya, Emory University; Bali Pulendran, Emory University
• Journal Title: Nature Immunology
• Volume: Volume 15, Number 2
• Publisher: Nature Publishing Group | 2014-02-01, Pages 195-204
• Type of Work: Article | Post-print: After Peer Review
• Publisher DOI: http://doi.org/10.1038/ni.2789
• Subjects: Health Sciences, Immunology; Biology, Microbiology; Health Sciences, Pathology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; REGULATORY NETWORKS; IMMUNE-SYSTEM; KINASE 1; VACCINOLOGY; EXPRESSION; VACCINATION; ACTIVATION; INFLUENZA; RECONSTRUCTION; PROTECTION

Abstract

Many vaccines induce protective immunity via antibodies. Systems biology approaches have been used to determine signatures that can be used to predict vaccine-induced immunity in humans, but whether there is a 'universal signature' that can be used to predict antibody responses to any vaccine is unknown. Here we did systems analyses of immune responses to the polysaccharide and conjugate vaccines against meningococcus in healthy adults, in the broader context of published studies of vaccines against yellow fever virus and influenza virus. To achieve this, we did a large-scale network integration of publicly available human blood transcriptomes and systems-scale databases in specific biological contexts and deduced a set of transcription modules in blood. Those modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines, which provided key insights into primary viral, protein recall and anti-polysaccharide responses. Our results elucidate the early transcriptional programs that orchestrate vaccine immunity in humans and demonstrate the power of integrative network modeling. © 2013 Macmillan Publishers Limited All rights reserved.