NOVEL APPROACH TO CHLAMYDIA VACCINE DEVELOPMENT

描述(申请人提供)：沙眼衣原体是美国性传播疾病(STD)的主要细菌原因，并继续在人群中传播，因为&gt；50%的感染者没有明显症状，无法获得治疗。这些未经治疗的衣原体感染会导致严重的并发症，包括盆腔炎、输卵管不孕和宫外孕，从而对妇女构成特别的健康风险。尽管这是一个高度优先的问题，但事实证明，很难设计出一种有效的沙眼衣原体疫苗。已有研究表明，T细胞对免疫保护是必要的，但它们也可能参与与发病机制相关的炎症。因此，阐明免疫T细胞在感染过程中的作用具有重要意义。虽然已有针对沙眼衣原体的T细胞克隆的报道，但很难获得足够数量的这种同源株来分析T细胞对这种病原体的反应谱。因此，我们利用T细胞杂交瘤技术，从阴道接种沙眼衣原体活菌的小鼠身上产生克隆的辅助T细胞(CD4+)和细胞毒性T细胞(CD8+)。T细胞杂交瘤将为我们提供一种独特的工具，用于鉴定沙眼衣原体的抗原，这些抗原能够在小鼠中引发广泛的T细胞反应。此外，通过与莱克兰空军基地威尔福德·霍尔医学中心的临床研究人员进行新的合作，将有可能评估感染衣原体的人的T细胞是否对在老鼠身上发现的相同抗原产生反应。这些目标代表了T细胞杂交瘤第一次被用于评估T细胞在感染活的衣原体后的激活情况，并将为提高对沙眼衣原体和其他细胞内病原体的免疫力的新方法提供重要的见解。

DESCRIPTION (provided by applicant): Chlamydia trachomatis is the leading bacterial cause of sexually transmitted disease (STD) in the United States and continues to spread in the population as >50% of the infected individuals show no overt symptoms and fail to obtain treatment. These untreated chlamydial infections pose a particular health risk in women by leading to severe complications including pelvic inflammation, tubal infertility, and ectopic pregnancy. Although a high priority, it has proven difficult to design an effective vaccine for Chlamydia trachomatis. It has been shown that T cells are necessary for immune protection, but they may also contribute to inflammation associated with pathogenesis. Thus, it is of great importance to delineate the roles of immune T cells during infection. Although T cell clones specific for C. trachomatis have been reported, it has been difficult to obtain sufficient numbers of such homogeneous lines to analyze the repertoire of the T cell response to this pathogen. Thus, we have exploited T cell hybridoma technology in order to generate panels of cloned helper (CD4 +) and cytotoxic (CD8 +) T cells from mice that had been vaginally inoculated with viable Chlamydia trachomatis. The T cell hybridomas will provide us with a unique tool for use in identifying the antigens from C. trachomatis that are capable of eliciting a broadbased T cell response in mice. In addition, through a new collaboration with clinical investigators at Wilford Hall Medical Center, Lackland Air Force Base, it will be possible to assess whether T cells from humans infected with Chlamydia respond to the same antigens that were identified in mice. These aims represent the first time that T cell hybridomas have been used to assess the activation of T cells in response to an infection with viable Chlamydia and should provide important insights into novel approaches for enhancing immunity to C. trachomatis and to other intracellular pathogens.