Investigation of novel chlamydia vaccines in male infection models and sexual transmission challenges

项目总结 沙眼衣原体(CT)是导致世界上最常见的细菌性传播的病原体 感染，2020年超过1.29亿例。未经治疗的泌尿生殖CT可能会有严重的后遗症，包括 盆腔炎、异位妊娠、输卵管因素不孕、附睾炎、尿道炎和前列腺炎。 未经治疗的肛门直肠CT可导致直肠炎、溃疡、脓肿、裂隙和瘘管。肛门直肠感染 可能也是细菌的储存库，在这种细菌中，通过自身接种发生泌尿生殖系统感染。MOST Ct 研究的重点是女性泌尿生殖系统感染，因为这些感染更常见地导致严重的 后遗症。然而，对男性沙眼衣原体感染的研究还有很大的差距和迫切的需要。虽然是男性 泌尿生殖道感染不太可能导致严重的后遗症，男性可以将感染传播给女性 生殖道，这是更容易发生并发症。此外，肛门直肠感染也发生在男性。 与男性发生性关系的人，与女性发生性关系的男性和女性。目前的治疗方法是根治的抗生素， 但这些并不能防止再感染，也不能有力地清除所有解剖部位的感染，而且可能会很差。 患者依从性。确定减少和预防CT传播以及限制感染的战略是 非常紧急。我们的实验室已经开发出使用高免疫原性噬菌体病毒的衣原体疫苗- 类颗粒(VLP)作为展示免疫原性Ct黏附因子短肽表位的平台 举止。特别是，我们的QB-VD4-MOMP疫苗，针对CT黏附因子主要外膜蛋白， 为雌性小鼠提供保护。然而，肛门直肠和男性泌尿生殖道有明显的区别 免疫环境以及这些部位的沙眼衣原体感染尚未得到很好的研究。这份F31提案旨在 研究我们的QB-VD4-MOMP疫苗对雄性小鼠预防衣原体感染的能力。这个 这项拟议研究的总体目标是确定这些疫苗的免疫原性和保护能力。 在雄性小鼠中，利用泌尿生殖、肛门直肠和性传播感染模型。这样做的结果是 研究将强调将通过预防感染和预防接种疫苗而受益的人群 变速箱。目的1研究疫苗对经泌尿生殖道或肛门直肠感染的雄性小鼠的免疫效果。 衣原体。此外，在任何一方或双方的免疫范围内，疫苗效力将是 衣原体在小鼠性传播模型中的研究(目标2)。这些疫苗可能会也可能不会引起 对男性和女性的保护相同，并使用佐剂、混合疫苗或替代疫苗 为了给男性提供保护，靶标可能是必要的。总的来说，这项研究将揭示以下重要方面 疫苗介导的保护，并使这些疫苗更接近人类临床试验。

PROJECT SUMMARY Chlamydia trachomatis (Ct) is the pathogen that causes the world’s most common bacterial sexually transmitted infection, with over 129 million cases in 2020. Untreated urogenital Ct can have severe sequelae, including pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, epididymitis, urethritis, and prostatitis. Untreated anorectal Ct can lead to proctitis, ulcerations, abscesses, fissures, and fistulas. Anorectal infections likely also act as a reservoir for the bacterium, in which urogenital infection occurs via autoinoculation. Most Ct research has focused on female urogenital infections, as these infections more commonly cause severe sequelae. However, there is a large gap and an urgent need to study Ct infections in males. Although male urogenital tract infections are less likely to lead to severe sequelae, males can transmit infection to the female reproductive tract, which is more vulnerable to complications. Additionally, anorectal infections occur in men who have sex with men, men who have sex with women and in women. Current treatment is curative antibiotics, but these do not prevent reinfection, do not robustly clear infection at all anatomic sites, and can have poor patient compliance. Identifying strategies to reduce and prevent transmission of Ct, as well as limit infection, is very urgent. Our lab has developed vaccines against Chlamydia using highly immunogenic bacteriophage virus- like particles (VLPs) as a platform displaying short peptide epitopes of Ct adhesion factors in an immunogenic manner. In particular, our Qb-VD4-MOMP vaccine, targeting Ct adhesion factor Major Outer Membrane Protein, provides protection in female mice. However, the anorectal tract and male urogenital tract have distinct immunological environments, and Ct infections at these sites are not well studied. This F31 proposal aims to investigate the ability of our Qb-VD4-MOMP vaccine to protect against Chlamydia infection in male mice. The overall goal of this proposed research is to determine the immunogenicity and protective ability of these vaccines in male mice, utilizing urogenital, anorectal, and sexual transmission infection models. The outcome of this research will highlight the populations that will benefit from vaccination by preventing both infection and transmission. Aim 1 will investigate vaccine efficacy in male mice urogenitally or anorectally infected with Chlamydia. Additionally, vaccine efficacy in the context of immunization of either or both partners will be investigated in mouse sexual transmission models of Chlamydia (Aim 2). These vaccines may or may not elicit the same protection in males as in females, and the use of adjuvants, mixed vaccines, or alternative vaccine targets may be necessary to provide protection in males. Overall, this research will reveal important aspects of vaccine-mediated protection and advance these vaccines closer to human clinical trials.