Human Responses to Candidate Chlamydial Antigens

沙眼衣原体(CT)是一种性传播细菌。每年有1亿人感染它。多数 感染没有任何症状，因此感染者得不到治疗。CT对女性的影响 是很严重的。大约每100例未经治疗的CT感染中就有1例导致不孕不育。女性的CT感染 也可能导致宫外孕和慢性盆腔疼痛。尽管需求巨大，但没有一种衣原体疫苗是 目前可用。这项研究计划更广泛的目标是加速开发一种新的 预防CT相关不孕症和其他疾病的疫苗。这项研究项目的目标是更好地 了解我们的免疫系统如何应对女性生殖道(FGT)中的CT复制。 FGT是我们身体中一个独特的器官。为了有效地发挥作用，FGT主动抑制免疫 回应。这个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细胞，称为T细胞。记忆T细胞可以检测和诱导 快速杀死被CT感染的细胞。在这里，我们将从两个方面研究CT复制和宿主T细胞反应 独特的女性群体。在第一个名为TRAC的队列中，对CT感染高危女性进行了12年的跟踪调查 月份。第二个队列，TRAC2，将在该项目期间建立，并将同样跟随妇女 沙眼衣原体感染的高风险。详细的临床和行为数据将从这两个队列中获得 参与者将被分成几组-抗CT组、CT易感组、CT感染但控制组 感染，CT感染合并播散性感染。关键是，来自血液和FGT的免疫细胞将 从我们的参与者那里收集并可供分析。 为了全面研究血液和FGT中T细胞在对抗CT感染中的作用，我们将 追求以下目标： 目标1.建立一种综合的方法来识别最有可能 有助于抗衣原体免疫。在这里，我们将进行第一次研究，以检查CT的表达 女性生殖道中的蛋白质。强表达的CT蛋白是很好的疫苗靶点。 目的2.表现出抵抗力的女性血液中对CT的保护性记忆T细胞反应特征 到CT再感染。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 对CT的指控。 目的3.比较和表征极限人群血液和FGT中T细胞的浸润性和驻留性 经历CT提升的女性感染宫颈内膜。在这里，我们将直接检查 CT感染能够限制细菌感染的女性FGT中T细胞的频率和功能 复制，未能限制感染的妇女，因此有患CT相关疾病的风险。

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.