The influence of rectal Chlamydia trachomatis infections on immunity and incident urogenital infections in women without an indication forrectal screening

直肠沙眼衣原体感染对无直肠筛查指征的女性免疫和泌尿生殖感染事件的影响

• 批准号: 10703789
• 负责人: Stephen J. Jordan
• 金额: $ 77.09万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-06 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10703789
• 关键词: Affect; Age; Age Years; Anal Sex; Animals; Antigens; Attenuated; Biological Assay; Blood; CD4 Positive T Lymphocytes; Cells; Cervical; Chlamydia; Chlamydia muridarum; Chlamydia trachomatis; Cytoprotection; Data; Development; Disease; Enrollment; Epidemiology; Etiology; Exhibits; Flow Cytometry; Foundations; Frequencies; Future; Gastrointestinal tract structure; Genitourinary System Infection; Genotype; Goals; High Risk Woman; Human; Immunity; In Vitro; Incidence; Individual; Infection; Inflammation; Interferon Type II; Knowledge; Mediating; Mononuclear; Mucosal Immunity; Mucous Membrane; Mus; Natural History; Nucleic Acid Amplification Tests; Oral; Oral Administration; Oral Sex; Organism; Outcome; Pathologic; Peripheral Blood Mononuclear Cell; Prevalence; Prospective, cohort study; Prostitution; Recommendation; Rectum; Risk; Sampling; Sex Behavior; Specimen; Stains; Swab; Symptoms; T cell response; T memory cell; T-Lymphocyte; Testing; Time; Tissues; Vaccines; Vagina; Woman; cell motility; chlamydia vaccine; clinically significant; cytokine; diaries; high risk; immunogenic; improved; infection risk; insight; memory CD4 T lymphocyte; mucosal vaccine; prospective; rectal; reproductive morbidity; routine screening; screening; screening guidelines; urogenital tract; vaccine development

ABSTRACT Chlamydia trachomatis (Ct) infections in the U.S. are increasing and no Ct vaccine exists. Annual urogenital tract (UGT) screening of <25 and high risk women of any age is recommended, but testing for rectal Ct infection is not recommended in women without rectal exposure. However, rectal Ct prevalence rates are similar in women regardless of anal sex exposures and up to 19% of Ct infections occur only in the rectum and would be missed by screening recommendations. Animal studies suggest that rectal infection is beneficial by inducing potent transmucosal immunity that protects the UGT against reinfection without pathological effects. It is critical that we understand whether rectal Ct infections in women are potentially harmful, by cross-contaminating the UGT, or beneficial, by inducing mucosal protection against UGT infection. Further, understanding if rectal Ct infections are immunogenic will establish if a mucosal chlamydia vaccine is feasible. We will enroll women at high-risk for chlamydia but who have never engaged in anal sex. Over 12 months, we will (1) obtain monthly oral, vaginal, and rectal swabs to detect incident Ct infections, (2) collect quarterly blood and cervical cytobrush specimens to study systemic and cervical T-cell responses, and (3) capture weekly sexual behavior and symptoms data to screen for exposure and Ct-related symptoms. The goal of this project is to test the hypothesis that (1) rectal Ct infections are frequent, long-lasting, asymptomatic, associated with specific rectal-tropic strains, and do not increase risk for UGT infection (Aim 1) and (2) assess their influence on systemic and cervical memory T-cell immunity and if they decrease incident UGT infections (Aim 2). By understanding if rectal Ct infections increase or decrease UGT infection risk, these studies may change screening guidelines and lay the foundation for development of an oral attenuated chlamydia vaccine.

摘要 美国的沙眼衣原体（Ct）感染正在增加，并且没有Ct疫苗存在。一年一次的泌尿生殖系统 建议对<25岁和任何年龄的高危妇女进行UGT筛查，但检测直肠Ct感染 不推荐用于没有直肠暴露的女性。然而，女性直肠Ct患病率相似， 不考虑肛交暴露，高达19%的Ct感染仅发生在直肠， 通过筛选推荐。动物研究表明，直肠感染是有益的，通过诱导强有力的 保护UGT免受再感染而无病理学影响的跨粘膜免疫。关键是我们 了解女性直肠Ct感染是否通过交叉污染UGT而具有潜在危害，或 有益的，通过诱导粘膜保护免受UGT感染。此外，了解直肠Ct感染 是否具有免疫原性将确定粘膜衣原体疫苗是否可行。我们将招募高风险的女性， 衣原体感染但从未进行过肛交的人在12个月内，我们将（1）每月获得口服，阴道， 和直肠拭子检测偶发Ct感染，（2）每季度采集血液和宫颈细胞刷标本， 研究全身和宫颈T细胞反应，以及（3）每周采集性行为和症状数据， 筛查暴露和CT相关症状本项目的目的是检验以下假设：（1）直肠Ct 感染是频繁的，持久的，无症状的，与特定的直肠嗜性菌株相关， 增加UGT感染风险（目的1）和（2）评估它们对全身和宫颈记忆T细胞的影响 免疫力，如果他们减少UGT感染事件（目标2）。通过了解直肠Ct感染是否增加 或降低UGT感染风险，这些研究可能会改变筛查指南，并为 研制口服减毒衣原体疫苗。