title: Unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology.
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.
authors.affiliation: Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Madelene
authors.initials: M
authors.lastname: Lindqvist
authors.forename: Intawat
authors.initials: I
authors.lastname: Nookaew
authors.forename: Ingrid
authors.initials: I
authors.lastname: Brinkenberg
authors.forename: Emma
authors.initials: E
authors.lastname: Samuelson
authors.forename: Karolina
authors.initials: K
authors.lastname: Thörn
authors.forename: Jens
authors.initials: J
authors.lastname: Nielsen
authors.forename: Ali M
authors.initials: AM
authors.lastname: Harandi
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000494:pharmacology*; D000282:Administration, Intravaginal; D000818:Animals; D001686:Biological Phenomena / Q000187:drug effects / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D007114:Immunization; D007249:Inflammation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D049490:Systems Biology / Q000379:methods*; D014621:Vagina / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism
chemical_list: D000276:Adjuvants, Immunologic