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Unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology

Journal article
Authors Madelene Lindqvist
Intawat Nookaew
Ingrid Brinkenberg
Emma Samuelson
Karolina Thörn
Jens B. Nielsen
Ali M Harandi
Published in PLoS ONE
Volume 6
Issue 6
Pages e20448
ISSN 1932-6203
Publication year 2011
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Institute of Biomedicine
Institute of Biomedicine, Department of Microbiology and Immunology
Pages e20448
Language en
Links dx.doi.org/10.1371/journal.pone.002...
https://gup.ub.gu.se/file/106541
Keywords Adjuvants, Immunologic, administration & dosage, pharmacology, Administration, Intravaginal, Animals, Biological Processes, drug effects, genetics, Female, Gene Expression Profiling, Gene Expression Regulation, drug effects, Immunization, Inflammation, genetics, Mice, Mice, Inbred C57BL, Signal Transduction, drug effects, genetics, Systems Biology, methods, Vagina, drug effects, immunology, metabolism
Subject categories Microbiology in the medical area

Abstract

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.

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