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Comparative Systems Analyses Reveal Molecular Signatures of Clinically tested Vaccine Adjuvants

T. A. Olafsdottir ; M. Lindqvist ; Intawat Nookaew (Institutionen för biologi och bioteknik, Systembiologi) ; P. Andersen ; J. Maertzdorf ; J. Persson ; D. Christensen ; Y. Zhang ; J. Anderson ; Sakda Khoomrung (Institutionen för biologi och bioteknik, Systembiologi) ; Partho Sarathi Sen ; E. M. Agger ; R. Coler ; D. Carter ; A. Meinke ; R. Rappuoli ; S. H. E. Kaufmann ; S. G. Reed ; A. M. Harandi
Scientific Reports (2045-2322). Vol. 6 (2016),
[Artikel, refereegranskad vetenskaplig]

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.

Nyckelord: t-cell responses, dendritic cells, tuberculosis vaccine, network, analysis, alum adjuvant, activation, immunity, generation, expression, infection, Science & Technology - Other Topics



Denna post skapades 2017-01-13. Senast ändrad 2017-02-03.
CPL Pubid: 246853

 

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Institutioner (Chalmers)

Institutionen för biologi och bioteknik, Systembiologi

Ämnesområden

Organisk kemi
Biokatalys och enzymteknik

Chalmers infrastruktur