Lorenzen Emma, Follmann Frank, Bøje Sarah, Erneholm Karin, Olsen Anja Weinreich, Agerholm Jørgen Steen, Jungersen Gregers, Andersen Peter
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.
Department of Infectious Disease Immunology, Chlamydia Vaccine Research, Statens Serum Institut , Copenhagen , Denmark.
Front Immunol. 2015 Dec 16;6:628. doi: 10.3389/fimmu.2015.00628. eCollection 2015.
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.
国际上在研发抗沙眼衣原体疫苗方面所做的努力凸显了采用新型免疫策略诱导生殖道免疫的必要性。在本研究中，我们在哥廷根小型猪模型中评估了一种肌肉注射（IM）初免/鼻内加强免疫接种策略，该模型的生殖系统与人类非常相似。疫苗由沙眼衣原体亚单位抗原组成，这些抗原用促进Th1/Th17的CAF01佐剂配制。用CAF01进行肌肉注射初免免疫诱导了显著的细胞介导的干扰素γ和白细胞介素17A反应以及显著的全身性高滴度中和性IgG反应。在生殖道受到攻击后，鼻内加强免疫的组产生了加速的、高度显著的生殖道IgA反应，这与感染后第3天细菌清除增强相关。通过检测抗原特异性分泌成分（SC），我们表明生殖道IgA是在生殖道黏膜局部产生的。阴道IgA SC反应与衣原体载量之间高度显著的负相关表明，小型猪模型中的IgA参与了对沙眼衣原体的保护。这对于我们理解保护性免疫以及未来针对沙眼衣原体和一般生殖道病原体的疫苗接种策略都很重要。
