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Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

Journal article
Authors Torunn Olafsdottir
Madelene Lindqvist
I. Nookaew
P. Andersen
J. Maertzdorf
Josefine Persson
D. Christensen
Yuan Zhang
Jenna Anderson
Sakda Khoomrung
E. M. Agger
R. Coler
D. Carter
A. Meinke
R. Rappuoli
S. H. E. Kaufmann
S. G. Reed
Ali M Harandi
Published in Scientific Reports
Volume 6
ISSN 2045-2322
Publication year 2016
Published at Institute of Biomedicine, Department of Microbiology and Immunology
Language en
Links dx.doi.org/10.1038/srep39097
Keywords t-cell responses, dendritic cells, tuberculosis vaccine, network, analysis, alum adjuvant, activation, immunity, generation, expression, infection, Science & Technology - Other Topics
Subject categories Clinical Medicine

Abstract

A better understanding of the mechanisms of action of human adjuvants could inform a rational development of next generation vaccines for human use. Here, we exploited a genome wide transcriptomics analysis combined with a systems biology approach to determine the molecular signatures induced by four clinically tested vaccine adjuvants, namely CAF01, IC31, GLA-SE and Alum in mice. We report signature molecules, pathways, gene modules and networks, which are shared by or otherwise exclusive to these clinical-grade adjuvants in whole blood and draining lymph nodes of mice. Intriguingly, co-expression analysis revealed blood gene modules highly enriched for molecules with documented roles in T follicular helper (TFH) and germinal center (GC) responses. We could show that all adjuvants enhanced, although with different magnitude and kinetics, TFH and GC B cell responses in draining lymph nodes. These results represent, to our knowledge, the first comparative systems analysis of clinically tested vaccine adjuvants that may provide new insights into the mechanisms of action of human adjuvants.

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