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

新型衣原体疫苗在男性感染模型和性传播挑战中的研究

• 批准号: 10750828
• 负责人: Andzoa Jamus
• 金额: $ 3.71万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10750828
• 关键词: Abscess; Adhesions; Adjuvant; Affect; Anatomy; Animal Model; Antibiotics; Antibody titer measurement; Anus; Bacteria; Bacteriophages; Biological Assay; Cell Culture Techniques; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Chronic; Clinical Trials; Data Analyses; Ectopic Pregnancy; Environment; Epididymitis; Epitopes; Exposure to; Fellowship; Female; Fissure in Ano; Fistula; Genital; Genitalia; Genitourinary System Infection; Genitourinary system; Goals; Histologic; Human; Immunization; Immunize; Immunologics; Infection; Investigation; Knowledge; Life Cycle Stages; Location; Luciferases; Mediating; Metabolic; Modeling; Mus; Outcomes Research; Pelvic Inflammatory Disease; Peptides; Phase; Population; Proctitis; Rectum; Research; Sexual Partners; Sexual Transmission; Sexually Transmitted Diseases; Site; Statistical Data Interpretation; Testing; Ulcer; Urethritis; Vaccinated; Vaccination; Vaccines; Virus-like particle; Woman; Work; chlamydia vaccine; compliance behavior; efficacy evaluation; immunogenic; immunogenicity; in vivo imaging system; infectious disease model; luciferin; major outer membrane protein; male; men; men who have sex with men; mouse model; novel; oral infection; pathogen; penis; prevent; prostatitis; rectal; reproductive tract; sex; sexually active; skills; transmission process; tubal infertility; urogenital tract; vaccine candidate; vaccine development; vaccine efficacy; vaccine immunogenicity; vaginal infection

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.

项目概要 沙眼衣原体 (Ct) 是导致世界上最常见的性传播细菌的病原体 感染，2020 年病例数将超过 1.29 亿。未经治疗的泌尿生殖 Ct 可能会产生严重的后遗症，包括 盆腔炎、宫外孕、输卵管因素不孕、附睾炎、尿道炎、前列腺炎。 未经治疗的肛门直肠CT可导致直肠炎、溃疡、脓肿、裂隙和肛门直肠感染。 也可能充当细菌的储存库，其中大多数 Ct 通过自身接种发生泌尿生殖感染。 研究重点是女性泌尿生殖系统感染，因为这些感染更常导致严重的 然而，尽管男性中的 Ct 感染存在很大的差距，但迫切需要研究。 泌尿生殖道感染不太可能导致严重后遗症，男性可将感染传染给女性 生殖道，更容易出现并发症。此外，男性也容易发生肛门直肠感染。 与男性发生性关系、男性与女性发生性关系以及女性的当前治疗方法是治疗性抗生素， 但这些方法并不能防止再感染，不能强有力地清除所有解剖部位的感染，并且可能效果不佳 确定减少和预防 Ct 传播以及限制感染的策略是患者的依从性。 非常紧迫。我们的实验室已经使用高免疫原性噬菌体病毒开发了针对衣原体的疫苗- 类颗粒（VLP）作为在免疫原性中展示 Ct 粘附因子短肽表位的平台 特别是我们的 Qb-VD4-MOMP 疫苗，针对 Ct 粘附因子主要外膜蛋白， 为雌性小鼠提供保护，然而，肛门直肠道和雄性泌尿生殖道具有不同的作用。 免疫环境和这些部位的 Ct 感染尚未得到充分研究。 研究我们的 Qb-VD4-MOMP 疫苗预防雄性小鼠衣原体感染的能力。 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得出了这一结果。 研究将重点关注通过预防感染和预防接种而受益的人群 目标 1 将研究泌尿生殖道或肛门直肠感染的雄性小鼠的疫苗功效。 此外，在一方或双方免疫的情况下，疫苗效力将受到影响。 在小鼠衣原体性传播模型中进行了研究（目标 2）。这些疫苗可能会或可能不会引起。 对男性和女性提供相同的保护，并使用佐剂、混合疫苗或替代疫苗 总体而言，这项研究将揭示男性的重要方面。 疫苗介导的保护并使这些疫苗更接近人体临床试验。