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- e20448

Areas of Advance

Life Science Engineering (2010-2018)

Subject Categories

Microbiology in the medical area

DOI

10.1371/journal.pone.0020448

PubMed

21666746

More information

Created

10/8/2017