Molecular signatures of antibody responses derived from a systems biological study of 5 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 W. 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 M Carlone, Centers for Disease Control and Prevention; 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 Imoto Nakaya, Emory University; Bali Pulendran, Emory University
• Journal Title: Nature Immunology
• Volume: Volume 15, Number 2
• Publisher: Nature Research (part of Springer Nature) | 2014-02, 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; Health Sciences, General

Abstract

Many vaccines induce protective immunity via antibodies. Recent studies have used systems biological approaches to determine signatures that predict vaccine immunity in humans, but whether there is a ‘universal signature’ that can predict antibody responses to any vaccine, is unknown. Here we performed systems analyses of immune responses to the meningococcal polysaccharide and conjugate vaccines in healthy adults, in the broader context of our previous studies with the yellow fever and two influenza vaccines. To achieve this, we performed a large-scale network integration of public human blood transcriptomes, and systems-scale databases in specific biological contexts, and deduced a set of blood transcription modules. These modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines providing key insights into primary viral, protein recall and anti-polysaccharide responses. These results illuminate the early transcriptional programs orchestrating vaccine immunity in humans, and demonstrate the power of integrative network modeling.