title: Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants.
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.
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Thorunn A
authors.initials: TA
authors.lastname: Olafsdottir
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Madelene
authors.initials: M
authors.lastname: Lindqvist
authors.affiliation: Department of Biology and Biological Engineering, Chalmers, University of Technology, Gothenburg, Sweden.|Department of Biomedical Informatics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA.
authors.forename: Intawat
authors.initials: I
authors.lastname: Nookaew
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Maertzdorf
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Josefine
authors.initials: J
authors.lastname: Persson
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Dennis
authors.initials: D
authors.lastname: Christensen
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Jenna
authors.initials: J
authors.lastname: Anderson
authors.affiliation: Department of Biology and Biological Engineering, Chalmers, University of Technology, Gothenburg, Sweden.
authors.forename: Sakda
authors.initials: S
authors.lastname: Khoomrung
authors.affiliation: Department of Biology and Biological Engineering, Chalmers, University of Technology, Gothenburg, Sweden.
authors.forename: Partho
authors.initials: P
authors.lastname: Sen
authors.affiliation: Department of Infectious Disease Immunology, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Else Marie
authors.initials: EM
authors.lastname: Agger
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Rhea
authors.initials: R
authors.lastname: Coler
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Darrick
authors.initials: D
authors.lastname: Carter
authors.affiliation: Valneva Austria GmbH, Campus Vienna Biocenter, Vienna, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Meinke
authors.affiliation: GSK Vaccines, Siena, Italy.
authors.forename: Rino
authors.initials: R
authors.lastname: Rappuoli
authors.affiliation: Department of Immunology, Max Planck Institute for Infection Biology, Berlin, Germany.
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Infectious Disease Research Institute, Seattle, Washington, USA.
authors.forename: Steven G
authors.initials: SG
authors.lastname: Reed
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Ali M
authors.initials: AM
authors.lastname: Harandi
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D004338:Drug Combinations; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks / Q000187:drug effects*; D018858:Germinal Center / Q000187:drug effects / Q000276:immunology*; D005960:Glucosides / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D008050:Lipid A / Q000008:administration & dosage* / Q000494:pharmacology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D013597:Systems Analysis; D049490:Systems Biology; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology*; D014611:Vaccination
chemical_list: D000276:Adjuvants, Immunologic; D004338:Drug Combinations; D005960:Glucosides; C544002:IC31 adjuvant; D008050:Lipid A; D009838:Oligodeoxyribonucleotides; D009842:Oligopeptides; C000608161:glucopyranosyl lipid-A