Unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology
Journal article, 2011
Sexually transmitted infections (STIs) unequivocally represent a major public health concern in both industrialized and developing countries. Previous efforts to develop vaccines for systemic immunization against a large number of STIs in humans have been unsuccessful. There is currently a drive to develop mucosal vaccines and adjuvants for delivery through the genital tract to confer protective immunity against STIs. Identification of molecular signatures that can be used as biomarkers for adjuvant potency can inform rational development of potent mucosal adjuvants. Here, we used systems biology to study global gene expression and signature molecules and pathways in the mouse vagina after treatment with two classes of experimental adjuvants. The Toll-like receptor 9 agonist CpG ODN and the invariant natural killer T cell agonist alpha-galactosylceramide, which we previously identified as equally potent vaginal adjuvants, were selected for this study. Our integrated analysis of genome-wide transcriptome data determined which signature pathways, processes and networks are shared by or otherwise exclusive to these 2 classes of experimental vaginal adjuvants in the mouse vagina. To our knowledge, this is the first integrated genome-wide transcriptome analysis of the effects of immunomodulatory adjuvants on the female genital tract of a mammal. These results could inform rational development of effective mucosal adjuvants for vaccination against STIs.
Administration
Immunologic
drug effects
drug effects
drug effects
Mice
Inflammation
genetics
methods
Signal Transduction
Intravaginal
immunology
Gene Expression Profiling
drug effects
pharmacology
genetics
Female
genetics
Gene Expression Regulation
metabolism
Inbred C57BL
Animals
Adjuvants
Immunization
Biological Processes
administration & dosage
Mice
Systems Biology
Vagina
Author
M. Lindqvist
University of Gothenburg
Intawat Nookaew
Chalmers, Chemical and Biological Engineering, Life Sciences
Ingrid Brinkenberg
University of Gothenburg
Emma Samuelson
University of Gothenburg
Karolina Thörn
University of Gothenburg
Jens B Nielsen
Chalmers, Chemical and Biological Engineering, Life Sciences
A. M. Harandi
University of Gothenburg
PLoS ONE
1932-6203 (ISSN) 19326203 (eISSN)
Vol. 6 6 e20448- e20448Areas of Advance
Life Science Engineering (2010-2018)
Subject Categories
Microbiology in the medical area
DOI
10.1371/journal.pone.0020448
PubMed
21666746