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性传播感染。
而未经治疗的感染是导致不良后遗症的主要原因,包括盆腔炎,
不孕不育和异位妊娠。筛查计划未能遏制不断上升的感染率。就像大多数
女性感染无症状,仅建议每年进行筛查,CT的发病率为
可能比报道的要高。虽然抗生素治疗是治愈的,但成功的生物医学预防策略是
缺乏。大多数CT自然病史研究在筛查和检查之间的短短1-2周时间内评估CT
随访治疗。很少有研究有更长的随访时间。总体而言,这些研究表明是自发的
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,其机制
人们对此了解甚少。阴道微生物群(VMB)是阻止CT感染的主要因素,而
VMB还可能通过减少CT的增殖和促进有效的免疫反应来帮助CT清除。
因此,确定可改变的阴道微环境特征在自发清除
CT可能导致新的介入治疗。本提案是为响应PA-19-096《控制
通过对自然历史的全面了解了解性传播感染(STI)
感染的可能性“。我们建议研究自发性CT清除与VMB的关系
(结构、功能、代谢体)、粘膜免疫和CT血清型特有特征。这项提议将
利用从阴道菌群纵向研究中收集的归档宫颈阴道灌洗液样本
3620名顺性女性接受了为期一年的季度跟踪调查。对样本进行回顾性CT筛查
研究结束后检测CT自发清除(n=311)和持续(n=321)
事件。具体的目标利用一个具有长期跟踪的存储库,并将评估可能推动
CT的自然历史:1)人口统计、临床和行为因素,2)阴道微生物组和
代谢体,3)粘膜炎症可溶性标志物,4)CT血清型组成。我们经验丰富的多面手
学科团队将适应、改进和应用现代方法在纵向流行病学中与机器-
学习和降维技术,以评估高维、多组数据。我们试图找出
与自发CT清除相关的免疫学、代谢学和细菌候选。这
对600多个存档样本进行的流行病学研究提供了确定疑似
自然清除和持久机制。分析结果将提供成本效益
为未来的验证性试验和实验机制研究提供理由。这一结果可能会导致新的CT
疫苗方法,通过确定针对临床相关血清型的保护相关因素并告知
选择最佳免疫反应的佐剂。这些数据也可能有助于抗生素节约的设计
方法,如活的生物治疗制剂,可以加强CT控制程序。
项目成果
期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
专利数量(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
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$ 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
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8042549 - 财政年份:2010
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