Cervicovaginal microbiome, mucosal immunity, and pathogen factors that contribute to spontaneous clearance of Chlamydia trachomatis
宫颈阴道微生物群、粘膜免疫和有助于沙眼衣原体自发清除的病原体因素
基本信息
- 批准号:10463072
- 负责人:
- 金额:$ 79.85万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-06-01 至 2026-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdjuvantAffectAgeAnimalsAnti-Inflammatory AgentsAntibiotic TherapyAntibioticsArchivesBacteriaBacterial VaginosisBehavioralBiogenic AminesBiologicalBiological Response Modifier TherapyCell AdhesionCharacteristicsChlamydiaChlamydia trachomatisClinicalCosts and BenefitsDataDevelopmentDimensionsEctopic PregnancyEpidemiologyEquilibriumEventFormulationFutureGenesGenitalGenitaliaGuidelinesHealth Care CostsHormonalHumanImmuneImmune responseImmunityImmunologic FactorsImmunologicsIn VitroIncidenceIndolesInfectionInfertilityInflammationInterferon Type IIInterleukin-10Interleukin-12Interleukin-2Interleukin-4Interleukin-6InterventionIrrigationIsomerismKynurenineLactic acidLactobacillusLeadLinkLongitudinal StudiesLubricantsMachine LearningMetagenomicsMethodsMissionModelingModernizationMucosal ImmunityMucous MembraneMultiomic DataMusNIH Program AnnouncementsNatural HistoryOrganismOutcomePathologicPelvic Inflammatory DiseasePersonal BehaviorPharmaceutical PreparationsPlayPrevention strategyPreventivePrevotellaRecording of previous eventsRecurrenceReportingResolutionResourcesRiskRoleSamplingSerotypingSexually Transmitted DiseasesSmokingStructureSystemT-LymphocyteTechniquesTh1 CellsTh2 CellsTryptophanUnited States National Institutes of HealthVaccine ResearchVaccinesVaginaVisitWomanWorkantibiotic designcervicovaginalcervicovaginal microbiomechronic pelvic paincis-femaleclinically relevantcohortconfirmatory trialenhancing factorepidemiology studyexperiencefollow-upguinea pig modelhigh dimensionalityimmunoregulationinfection rateinflammatory markermajor outer membrane proteinmetabolomemetabolomicsmultidisciplinarynovelnovel strategiespathogenpreventprogramsrepositoryresponseroutine Bacterial stainsample archivescreeningscreening programsuccessful interventionvaccine trialvaginal microbiomevaginal microbiotayoung woman
项目摘要
Chlamydia trachomatis (CT) is the most commonly reported bacterial sexually transmitted infection in the U.S.
and untreated infections are a major cause of adverse sequelae, including pelvic inflammatory disease,
infertility, and ectopic pregnancy. Screening programs have failed to curb rising infection rates. As most
infections in women are asymptomatic and screening is only recommended annually, the incidence of CT is
likely higher than reported. While antibiotic therapy is curative, successful biomedical prevention strategies are
lacking. Most CT natural history studies evaluate CT in the short 1-2 week interval between screening and
follow-up for treatment. Few studies have had longer follow-up. Overall, these studies suggest spontaneous
clearance of CT (in the absence of antibiotic treatment) occurs in 11-44% of cases; however, the mechanisms
are poorly understood. The vaginal microbiome (VMB) is a major factor in preventing CT acquisition, and the
VMB may also aid in CT clearance by reducing CT proliferation and promoting effective immune responses.
Thus, identifying modifiable vaginal microenvironmental features that play a role in spontaneous clearance of
CT may lead to novel interventions. This proposal is submitted in response to PA-19-096 “Control of
Sexually Transmitted Infections (STIs) Through a Comprehensive Understanding of the Natural History
of Infection”. We propose to investigate the relations between spontaneous CT clearance and VMB
(structure, function, metabolome), mucosal immunity, and CT serovar-specific features. This proposal will
utilize archived cervicovaginal lavage samples collected from the Longitudinal Study of Vaginal Flora in which
3,620 cisgender women were followed quarterly for one year. Samples were retrospectively screened for CT
after the study concluded and detected CT spontaneous clearance (n=311) and persistence (n=321)
events. The specific aims utilize a repository with a long follow-up and will assess four domains that may drive
the natural history of CT: 1) demographic, clinical, and behavioral factors, 2) vaginal microbiome and
metabolome, 3) mucosal soluble markers of inflammation, 4) CT serovar composition. Our experienced, multi-
disciplinary team will adapt, refine, and apply modern methods in longitudinal epidemiology with machine-
learning and dimension-reduction techniques to assess high-dimensional, multi-omic data. We seek to identify
immunologic, metabolomic, and bacterial candidates that are associated with spontaneous CT clearance. This
epidemiologic study of over 600 archived samples presents the best available resource for identifying likely
natural clearance and persistence mechanisms. Findings from the analyses would provide the cost-benefit
justification for future confirmatory trials and experimental mechanistic studies. The results may lead to new CT
vaccine approaches by pinpointing correlates of protection against clinically-relevant serovars and informing
choice of adjuvants for optimal immune response. The data may also aid the design of antibiotic-sparing
approaches, such as live biotherapeutic formulations, which could enhance CT control programs.
沙眼衣原体(CT)是美国最常见的细菌性传播感染。
未经治疗的感染是不良后遗症的主要原因,包括盆腔炎,
不孕和宫外孕。筛查计划未能遏制感染率的上升。因为大多数
女性感染无症状,仅建议每年进行筛查,CT的发病率为
可能比报告的要高。虽然抗生素治疗是治愈性的,但成功的生物医学预防策略
缺乏大多数CT自然史研究在筛选和治疗之间的1-2周间隔内评价CT。
随访治疗。很少有研究有更长的随访时间。总的来说,这些研究表明,
CT的清除(在没有抗生素治疗的情况下)发生在11-44%的病例中;然而,
我们对此知之甚少。阴道微生物组(VMB)是阻止CT采集的主要因素,
VMB还可以通过减少CT增殖和促进有效的免疫应答来帮助CT清除。
因此,确定在自发清除中起作用的可改变的阴道微环境特征,
CT可能导致新的干预措施。本提案是根据PA-19-096“控制
性传播感染(STIs)通过全面了解自然史
感染”。我们建议研究自发CT清除和VMB之间的关系
(结构、功能、代谢组)、粘膜免疫和CT血清型特异性特征。这项建议会
利用从阴道植物群纵向研究中收集的存档宫颈阴道灌洗样本,其中
每季度对3,620名顺性别妇女进行为期一年的跟踪调查。对样本进行回顾性CT筛查
研究结束后,检测到CT自发清除(n=311)和持续性(n=321)
事件具体目标利用一个长期跟踪的知识库,并将评估可能推动
CT的自然史:1)人口统计学、临床和行为因素,2)阴道微生物组,
代谢物组,3)粘膜可溶性炎症标志物,4)CT血清型组成。我们经验丰富的,多-
学科团队将适应,完善和应用现代方法在纵向流行病学与机器,
学习和降维技术来评估高维,多组学数据。我们试图找出
免疫学、代谢组学和细菌候选物与自发CT清除相关。这
对600多个存档样本的流行病学研究为确定可能的
自然清除和持久性机制。分析结果将提供成本效益
未来验证性试验和实验机制研究的理由。结果可能导致新的CT
通过精确定位临床相关血清型的保护相关因素,
选择最佳免疫应答的佐剂。这些数据还可以帮助设计防腐蚀的
这些方法,如活的生物制剂,可以增强CT控制程序。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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REBECCA M. BROTMAN其他文献
REBECCA M. BROTMAN的其他文献
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{{ truncateString('REBECCA M. BROTMAN', 18)}}的其他基金
Cervicovaginal microbiome, mucosal immunity, and pathogen factors that contribute to spontaneous clearance of Chlamydia trachomatis
宫颈阴道微生物群、粘膜免疫和有助于沙眼衣原体自发清除的病原体因素
- 批准号:
10631994 - 财政年份:2022
- 资助金额:
$ 79.85万 - 项目类别:
Methods to Test the Role of Age-related Lifestyle and Vaginal Microenvironment Changes and the Prevention, Treatment, and Progression of Genitourinary Syndrome of Menopause
测试与年龄相关的生活方式和阴道微环境变化以及更年期泌尿生殖综合征的预防、治疗和进展的作用的方法
- 批准号:
10475571 - 财政年份:2021
- 资助金额:
$ 79.85万 - 项目类别:
Methods to Test the Role of Age-related Lifestyle and Vaginal Microenvironment Changes and the Prevention, Treatment, and Progression of Genitourinary Syndrome of Menopause
测试与年龄相关的生活方式和阴道微环境变化以及更年期泌尿生殖综合征的预防、治疗和进展的作用的方法
- 批准号:
10675518 - 财政年份:2021
- 资助金额:
$ 79.85万 - 项目类别:
Methods to Test the Role of Age-related Lifestyle and Vaginal Microenvironment Changes and the Prevention, Treatment, and Progression of Genitourinary Syndrome of Menopause
测试与年龄相关的生活方式和阴道微环境变化以及更年期泌尿生殖综合征的预防、治疗和进展的作用的方法
- 批准号:
10091738 - 财政年份:2021
- 资助金额:
$ 79.85万 - 项目类别:
Methods to Test Lifestyle, Vaginal Microenvironment, and Genitourinary Symptoms across Menopause Transition
测试更年期过渡期间生活方式、阴道微环境和泌尿生殖系统症状的方法
- 批准号:
10229293 - 财政年份:2020
- 资助金额:
$ 79.85万 - 项目类别:
Longitudinal Study of the Vaginal Microbiome Prior To Incident STI
性传播感染发生前阴道微生物组的纵向研究
- 批准号:
8963646 - 财政年份:2015
- 资助金额:
$ 79.85万 - 项目类别:
Vaginal microbiota, immune responses and vulvovaginal symptoms during menopause
更年期期间的阴道微生物群、免疫反应和外阴阴道症状
- 批准号:
8721849 - 财政年份:2013
- 资助金额:
$ 79.85万 - 项目类别:
Vaginal microbiota, immune responses and vulvovaginal symptoms during menopause
更年期期间的阴道微生物群、免疫反应和外阴阴道症状
- 批准号:
8568384 - 财政年份:2013
- 资助金额:
$ 79.85万 - 项目类别:
Molecular Epidemiology of the Vaginal Microbiome
阴道微生物组的分子流行病学
- 批准号:
8042549 - 财政年份:2010
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$ 79.85万 - 项目类别:
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