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

Li S1, Rouphael N2, Duraisingham S1, Romero-Steiner S3, Presnell S4, Davis C5, Schmidt DS3, Johnson SE3, Milton A3, Rajam G3, Kasturi S6, Carlone GM3,Quinn C4, Chaussabel D4, Palucka AK7, Mulligan MJ8, Ahmed R9, Stephens DS5, Nakaya HI10, Pulendran B10.

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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.