title: Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis.
abstract: International efforts in developing a vaccine against Chlamydia trachomatis have highlighted the need for novel immunization strategies for the induction of genital immunity. In this study, we evaluated an intramuscular (IM) prime/intranasal boost vaccination strategy in a Göttingen Minipig model with a reproductive system very similar to humans. The vaccine was composed of C. trachomatis subunit antigens formulated in the Th1/Th17 promoting CAF01 adjuvant. IM priming immunizations with CAF01 induced a significant cell-mediated interferon gamma and interleukin 17A response and a significant systemic high-titered neutralizing IgG response. Following genital challenge, intranasally boosted groups mounted an accelerated, highly significant genital IgA response that correlated with enhanced bacterial clearance on day 3 post infection. By detecting antigen-specific secretory component (SC), we showed that the genital IgA was locally produced in the genital mucosa. The highly significant inverse correlation between the vaginal IgA SC response and the chlamydial load suggests that IgA in the minipig model is involved in protection against C. trachomatis. This is important both for our understanding of protective immunity and future vaccination strategies against C. trachomatis and genital pathogens in general.
authors.affiliation: Section for Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Emma
authors.initials: E
authors.lastname: Lorenzen
authors.affiliation: Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens Serum Institut , Copenhagen , Denmark.
authors.forename: Frank
authors.initials: F
authors.lastname: Follmann
authors.affiliation: Section for Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bøje
authors.affiliation: Section for Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Karin
authors.initials: K
authors.lastname: Erneholm
authors.affiliation: Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens Serum Institut , Copenhagen , Denmark.
authors.forename: Anja Weinreich
authors.initials: AW
authors.lastname: Olsen
authors.affiliation: Section for Veterinary Reproduction and Obstetrics, Department of Large Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen , Copenhagen , Denmark.
authors.forename: Jørgen Steen
authors.initials: JS
authors.lastname: Agerholm
authors.affiliation: Section for Immunology and Vaccinology, National Veterinary Institute, Technical University of Denmark , Copenhagen , Denmark.
authors.forename: Gregers
authors.initials: G
authors.lastname: Jungersen
authors.affiliation: Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens Serum Institut , Copenhagen , Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Andersen
keywords: Chlamydia trachomatis; intranasal immunization; minipig model; mucosal immunity; mucosal vaccination/immunization; vaccination strategy; vaccine