unraveling molecular signatures of immunostimulatory adjuvants in the female genital tract through systems biology揭示女性生殖道免疫刺激性佐剂的分子签名通过系统生物学.pdf

Unraveling Molecular Signatures of Immunostimulatory Adjuvants in the Female Genital Tract through Systems Biology 1. 2. 1 1 ¨ 1 Madelene Lindqvist , Intawat Nookaew , Ingrid Brinkenberg , Emma Samuelson , Karolina Thorn , 2 1 Jens Nielsen , Ali M. Harandi * 1 Department of Microbiology and Immunology, Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden, 2 Department of Chemical and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden 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