A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants
Tekijät: Olafsdottir TA, Lindqvist M, Nookaew I, Andersen P, Maertzdorf J, Persson J, Christensen D, Zhang Y, Anderson J, Khoomrung S, Sen P, Agger EM, Coler R, Carter D, Meinke A, Kaufmann SH, Rappuoli R, Harandi AM, Reed SG
Julkaisuvuosi: 2016
Tietokannassa oleva lehden nimi: Scientific reports
Lehden akronyymi: Sci Rep
Vuosikerta: 6
Sivujen määrä: 14
ISSN: 2045-2322
eISSN: 2045-2322
DOI: https://doi.org/10.1038/srep39097
Tiivistelmä
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.
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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