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.

项目摘要 衣原体沙眼（CT）是导致世界上最常见细菌性传播的病原体 感染，2020年有超过1.29亿例病例。未经处理的泌尿生殖器CT可能具有严重的后遗症，包括 盆腔炎症性疾病，异位妊娠，输卵管不育症，附睾炎，尿道炎和前列腺炎。 未经治疗的厌取性CT会导致直肠炎，溃疡，脓肿，裂缝和瘘管。厌食症感染 也可能充当细菌的储层，其中泌尿生殖器感染通过自身启动。大多数CT 研究重点是女性泌尿生殖器感染，因为这些感染更常见 后遗症。但是，存在很大的差距，迫切需要研究男性的CT感染。虽然男性 泌尿生殖道感染不太可能导致严重的后遗症，雄性可以将感染传播给女性 生殖道，更容易受到并发症的影响。另外，男性发生厌食症感染 与男人发生性关系的男人，与女人发生性关系的男人。当前治疗是治愈性抗生素， 但是，这些不会阻止再感染，在所有解剖部位都不会强烈清除感染，并且可能很差 患者合规性。确定减少和防止CT的传播以及极限感染的策略是 非常紧急。我们的实验室已使用高度免疫原性噬菌体病毒开发了针对衣原体的疫苗 像颗粒（VLP）一样，作为一个平台，显示出免疫原性中CT粘合剂的短肽表位 方式。特别是，我们的QB-VD4-Momp疫苗针对CT粘合因子主要外膜蛋白， 为雌鼠提供保护。但是，厌食症和雄性泌尿生殖道具有不同的 这些部位的免疫学环境和CT感染并不很好。该F31提议旨在 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 这项拟议的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，使用泌尿生殖器，厌食和性传播感染模型。结果的结果 研究将强调通过防止感染和 传播。 AIM 1将研究泌尿生成型雄性小鼠的疫苗效率或垂直于感染的 衣原体。此外，在任何一个或两个伴侣免疫的背景下的疫苗效率将是 在小鼠性传播模型中进行了研究（AIM 2）。这些疫苗可能会或可能不会引起 男性的保护与女性相同，以及使用调节剂，混合疫苗或替代疫苗的使用 对于男性提供保护可能是必要的。总体而言，这项研究将揭示 疫苗介导的保护并推进这些疫苗，更接近人类的临床试验。