Human Responses to Candidate Chlamydial Antigens

人类对候选衣原体抗原的反应

基本信息

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
项目类别：
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

项目摘要

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，每年感染 1 亿人。感染没有任何症状，因此感染者无法接受 CT 治疗。大约每 100 例未经治疗的 CT 感染就会导致女性不孕。还可能导致宫外孕和慢性盆腔疼痛，尽管有很大的需求，但目前还没有衣原体疫苗。目前该研究计划的更广泛目标是加速小说的开发。该研究项目的目标是更好地预防 CT 相关的不孕症和其他疾病。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 是我们体内独特的器官，为了有效发挥功能，FGT 会主动抑制免疫。该研究项目的基本原理是控制 CT 复制需要有效的免疫。血液和女性生殖道中的记忆 T 细胞都可以检测和诱导。在这里，我们将研究 CT 复制和宿主 T 细胞反应的两个方面。在第一个称为 TRAC 的独特女性队列中，对 CT 感染高风险的女性进行了 12 次随访。第二个队列 TRAC2 将在该项目期间建立，并将同样跟踪患有此类疾病的女性。 CT 感染的高风险将从两个队列中获得详细的临床和行为数据。参与者被分为几组——CT 耐药组、CT 易感组、CT 感染但控制组严重的是，来自血液和 FGT 的免疫细胞都将被感染。从我们的参与者那里收集并可供分析。为了全面检查 T 细胞在血液和 FGT 中的作用，在对抗 CT 感染中，我们将追求以下目标：目标 1. 建立一种综合方法来鉴定最有可能的衣原体抗原在这里，我们将进行第一项研究来检查 CT 的表达女性生殖道中强烈表达的 CT 蛋白是疫苗的绝佳靶点。目标 2. 表征表现出耐药性的女性血液中保护性记忆 T 细胞对 CT 的反应在这里，我们的目标是确定血液中提供抵抗力的 T 细胞的类型和功能。反对CT。目标 3. 比较和表征限制性女性的血液中的浸润性和驻留性 T 细胞以及 FGT 经历过CT提升的女性是否有宫颈内膜感染？在这里，我们将直接检查宫颈内膜感染。感染 CT 的女性 FGT 中 T 细胞的频率和功能能够限制细菌无法限制感染并因此面临 CT 相关疾病风险的女性。