Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

• DOI: 10.1038/srep39097
• Publication Date: 2016-12-13T10:23:39Z
• Authors: Thorunn A. Olafsd...; Madelene Lindqvist; Intawat Nookaew; Peter Andersen; Jeroen Maertzdorf; Josefine Persson; Dennis Christensen; Yuan Zhang; Jenna Anderson; Sakda Khoomrung; Partho Sen; Else Marie Agger; Rhea Coler; Darrick Carter; Andreas Meinke; Rino Rappuoli; Stefan H. E. Kauf...; Steven G. Reed; Ali M. Harandi
• Keywords: Systems Analysis; Gene Expression Profiling; Systems Biology; Vaccination; T-Lymphocytes, Helper-Inducer; Adaptive Immunity; Germinal Center; Article; 3. Good health; Drug Combinations; 03 medical and health sciences; Lipid A; 0302 clinical medicine; Adjuvants, Immunologic; Gene Expression Regulation; Glucosides; Oligodeoxyribonucleotides; Animals; Humans; Gene Regulatory Networks; Oligopeptides

AbstractA 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.