Intramuscular Priming and Intranasal Boosting Induce Strong Genital Immunity Through Secretory IgA in Minipigs Infected with Chlamydia trachomatis.

Emma Lorenzen,Anja Weinreich Olsen,Karin Erneholm,Peter Andersen,Jørgen Steen Agerholm,Sarah Bøje,Gregers Jungersen,Frank Follmann

doi:10.3389/fimmu.2015.00628

Emma Lorenzen, Anja Weinreich Olsen + Show 6 more

Open Access

https://doi.org/10.3389/fimmu.2015.00628

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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.

Highlights

Most of all human infections are established at the mucosal surfaces [1], including sexually transmitted infections with Chlamydia trachomatis, the most common sexually transmitted bacterium globally
It is becoming increasingly clear that mucosal IgA and IgG antibodies represent an important part of the protective immune response against genital C. trachomatis infection [8, 10, 11, 39, 40]
We demonstrate that an immunization strategy with IM priming and IN boosting, results in a strong significant secretory IgA (SIgA) response in the genital tract of female minipigs following genital challenge and that the local SIgA response appears to be important for an accelerated clearance of a genital C. trachomatis infection

Summary

Introduction

Most of all human infections are established at the mucosal surfaces [1], including sexually transmitted infections with Chlamydia trachomatis, the most common sexually transmitted bacterium globally. C. trachomatis is a major global health problem causing more than 100 million new cases of genital chlamydia each year [2]. Untreated infections can cause severe permanent complications, such as pelvic inflammatory disease, ectopic pregnancy, and infertility in women [3]. Screening programs and treatments have been intensified to lower the prevalence of C. trachomatis infections, largely without the expected impact on the incidence of C. trachomatis cases. Large international efforts are focused on the development of a vaccine [3,4,5,6]

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