Human Responses to Candidate Chlamydial Antigens

人类对候选衣原体抗原的反应

• 批准号: 10615096
• 负责人: Toni Darville
• 金额: $ 98.29万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10615096
• 关键词: Acceleration; Address; Age; Antibodies; Antibody Response; Antigens; Bacteria; Behavioral; Blood; CD8-Positive T-Lymphocytes; Cells; Cervical; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Classification; Clinical; Clinical Research; Data; Dedications; Development; Disease; Ectopic Pregnancy; Endocervix; Endometrial; Endometrium; Environment; Exhibits; Female; Female genitalia; Frequencies; Genital; Genitalia; Goals; High Risk Woman; Human; Immune; Immune response; Immune system; Immunity; Immunobiology; Infection; Infection Control; Infertility; Infiltration; Knowledge; Left; Lymphoid Tissue; Maps; Mediating; Mediation; Mucous Membrane; Natural Immunity; North Carolina; Organ; Participant; Pathogenesis; Persons; Phenotype; Predisposition; Productivity; Proteins; Proteomics; Public Health; Regimen; Research; Research Project Grants; Resistance; Risk; Role; Serology; Sexual Transmission; Subunit Vaccines; Symptoms; T cell infiltration; T cell response; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Techniques; Tissues; Transcript; Universities; Vaccine Antigen; Vaccine Design; Vaccines; Woman; chlamydia vaccine; chronic pelvic pain; cohort; deep sequencing; design; experience; high risk; immunogenicity; men; mouse model; novel; novel vaccines; prevent; programs; reproductive; reproductive tract; response; time of flight mass spectrometry; transcriptome; transcriptome sequencing; vaccine development; vaccine evaluation; Acceleration; Address; Age; Antibodies; Antibody Response; Antigens; Bacteria; Behavioral; Blood; CD8-Positive T-Lymphocytes; Cells; Cervical; Chlamydia; Chlamydia Infections; Chlamydia trachomatis; Classification; Clinical; Clinical Research; Data; Dedications; Development; Disease; Ectopic Pregnancy; Endocervix; Endometrial; Endometrium; Environment; Exhibits; Female; Female genitalia; Frequencies; Genital; Genitalia; Goals; High Risk Woman; Human; Immune; Immune response; Immune system; Immunity; Immunobiology; Infection; Infection Control; Infertility; Infiltration; Knowledge; Left; Lymphoid Tissue; Maps; Mediating; Mediation; Mucous Membrane; Natural Immunity; North Carolina; Organ; Participant; Pathogenesis; Persons; Phenotype; Predisposition; Productivity; Proteins; Proteomics; Public Health; Regimen; Research; Research Project Grants; Resistance; Risk; Role; Serology; Sexual Transmission; Subunit Vaccines; Symptoms; T cell infiltration; T cell response; T memory cell; T-Lymphocyte; T-Lymphocyte Subsets; Techniques; Tissues; Transcript; Universities; Vaccine Antigen; Vaccine Design; Vaccines; Woman; chlamydia vaccine; chronic pelvic pain; cohort; deep sequencing; design; experience; high risk; immunogenicity; men; mouse model; novel; novel vaccines; prevent; programs; reproductive; reproductive tract; response; time of flight mass spectrometry; transcriptome; transcriptome sequencing; vaccine development; vaccine evaluation

Chlamydia trachomatis (CT) is a sexually transmitted bacteria. Each year it infects 100 million people. Most infections do not have any symptoms so infected people are left untreated. In women the consequences of CT are severe. Approximately, 1 in every 100 untreated CT infections results in infertility. CT infections in women can also result in ectopic pregnancy and chronic pelvic pain. Despite the great need, no chlamydial vaccine is currently available. The broader goal of this research program is to accelerate development of a novel vaccine that prevents CT-associated infertility and other disease. The goal of this research project is to better understand how our immune system responds to CT replication in the female genital tract (FGT). The FGT is a unique organ in our body. To effectively function, the FGT actively suppresses immune responses. The rationale of this research project is that control of CT replication requires effective immune cells, called T cells, both in the blood and in the female genital tract. Memory T cells can detect and induce rapid killing of CT-infected cells. Here, we will investigate CT replication and the host T cell response in two unique female cohorts. In the first cohort called TRAC, women at high risk of CT infection were followed for 12 months. The second cohort, TRAC2, will be established during this project and will similarly follow women with high risk of CT infection. Detailed clinical and behavioral data will be available from both cohorts enabling participants to be classified into several groups – CT-resistant, CT-susceptible, CT-infected but controlling infection, CT-infected with disseminated infection. Critically, immune cells from both blood and the FGT will be collected from our participants and available for analysis. To comprehensively examine the role of T cells both in the blood and FGT, in combatting CT infection we will pursue the following aims: Aim 1. Establish a comprehensive approach to identify chlamydial antigens that would be most likely to contribute to anti-chlamydial immunity. Here we will perform the first study to examine expression of CT proteins in a woman’s female genital tract. Strongly expressed CT proteins are excellent targets for vaccines. Aim 2. Characterize the protective memory T cell response to CT in the blood of women who exhibit resistance to CT reinfection. Here, we aim to identify the types and functions of T cells in the blood that provide resistance against CT. Aim 3. Compare and characterize infiltrating and resident T cells in the blood and FGT of women who limit infection to the endocervix with women who experience CT ascension. Here, we will directly examine the frequency and function of T cells in the FGT of women who whilst CT infected are able to limit bacterial replication, with women who fail to limit infection and are therefore at risk of CT-associated disease.

沙眼衣原体（CT）是一种性传播细菌。每年它感染了1亿人。最多 感染没有任何符号，因此受感染的人未经治疗。在女性中，CT的后果 很严重。大约有100个未处理的CT感染中有1个导致不育。女性的CT感染 也可能导致生态妊娠和慢性骨盆疼痛。尽管有很大的需求，但没有衣原体疫苗是 目前可用。该研究计划的更广泛的目标是加快小说的发展 防止CT相关的不育症和其他疾病的疫苗。该研究项目的目的是改善 了解我们的免疫系统如何响应女性生殖道（FGT）中的CT复制。 FGT是我们体内的独特器官。为了有效发挥作用，FGT积极抑制免疫 回答。该研究项目的理由是，控制CT复制需要有效的免疫 在血液和女性生殖道中，称为T细胞，称为T细胞。记忆T细胞可以检测和影响 快速杀死CT感染的细胞。在这里，我们将研究CT复制和宿主T细胞响应。 独特的女同伙。在第一个称为TRAC的队列中，患有CT感染高风险的妇女进行12 月份。第二个队列TRAC2将在此项目期间建立，并将同样跟随妇女 CT感染的高风险。详细的临床和行为数据将从两个同类群体中获得 参与者将分为几个组 - 耐CT，可见的，CT感染但控制的参与者 感染，CT感染了传播感染。至关重要的是，血液和FGT的免疫细胞将是 从我们的参与者那里收集，可用于分析。 为了全面检查T细胞在血液和FGT中的作用，在打击CT感染中，我们将 追求以下目的： 目标1。建立一种识别最有可能最有可能的衣原体抗原的综合方法 有助于抗神经免疫。在这里，我们将进行第一项研究以检查CT的表达 女性女性生殖道中的蛋白质。强烈表达的CT蛋白是疫苗的极好靶标。 目标2。表征暴露阻力的女性血液中对CT的保护性记忆T细胞反应 重新感染。在这里，我们旨在确定血液中T细胞的类型和功能，以提供抗药性 反对CT。 目标3。比较和表征浸润和居民T细胞在限制的妇女的血液和FGT中 与经历CT提升的妇女感染了内部。在这里，我们将直接检查 未感染CT的女性FGT中T细胞的频率和功能能够限制细菌 复制，未能限制感染并且有与CT相关疾病的风险的妇女。