Immunity to Chlamydial Genital Infection

描述（由申请人提供）：尽管我们对这种细菌病原体的发病机制和流行病学的了解取得了重大进展，但沙眼衣原体性传播感染在世界范围内引起了相当大的发病率和社会经济负担。泌尿生殖道衣原体感染很容易用抗生素治愈，但由于无症状感染的频率和诊断延误，仅基于抗菌化疗的控制措施受到阻碍。通过研制安全有效的疫苗，最终控制沙眼衣原体性传播疾病是可能的。在过去的十年中，通过使用小鼠感染衣原体模型的研究，人们对衣原体生殖器感染的保护性免疫有了更高的了解。从使用小鼠感染模型的研究中获得的见解具有相当大的兴趣，因为它们为开发有效的疫苗提供了希望。利用小鼠生殖道衣原体感染模型，我们已经证明抗衣原体抗体在生殖道再感染中具有明显的保护作用。在我们提出的研究中，我们将通过4个特定目标进一步定义和表征保护性抗体介导的反应。目的1侧重于通过确定抗体治疗（恢复期血清）的最佳时机和剂量来优化反应；Aim 2使用免疫组学方法鉴定由保护性恢复期血清识别的衣原体抗原；在Aim 3中，我们将测试在Aim 2中鉴定的保护性抗原的重组制剂诱导保护性抗体反应的能力；最后，我们已经证明抗体的保护作用依赖于尚未确定的细胞群，在Aim 4中，我们将开始表征与保护性抗体相互作用以解决继发性衣原体再感染的细胞成分。只有开发出有效的疫苗，才能持续控制衣原体泌尿生殖系统感染。本建议中概述的研究将为实现这一目标提供重要的见解。

DESCRIPTION (provided by applicant): Chlamydia trachomatis sexually transmitted infections cause considerable morbidity and socioeconomic burden worldwide, despite significant advances in our understanding of the pathogenesis and epidemiology of this bacterial pathogen. Chlamydial urogenital infections are readily cured with antibiotics, but control measures based upon antimicrobial chemotherapy alone are hampered by the frequency of asymptomatic infections and delayed diagnosis. Definitive control of C. trachomatis sexually transmitted diseases is possible through the development of a safe and effective vaccine. A heightened understanding of protective immunity to chlamydial genital infection has emerged this past decade from studies using a mouse model of Chlamydia muridarum infection. The insights gained from studies using the mouse model of infection are of considerable interest because they offer promise for the development of an efficacious vaccine. Using the mouse model of chlamydial genital infection, we have shown that anti-chlamydia antibody markedly protects animals during genital tract reinfection. In our proposed studies we will further define and characterize the protective antibody-mediated response through 4 specific aims. Aim 1 focuses on optimizing the response by determining the optimum timing and dose of antibody therapy (convalescent serum); Aim 2 uses an immunomics approach to identify chlamydial antigens recognized by the protective convalescent serum; in Aim 3 we will test recombinant preparations of protective antigens identified in Aim 2 for their ability to induce protective antibody responses; and lastly, we have shown that the protective effect of antibody is dependent on a yet to be identified cell population and in Aim 4 we will begin to characterize the cellular component that interacts with protective antibody to resolve secondary chlamydial reinfection. Sustained control of chlamydial urogenital infections will be achieved only by the development of an efficacious vaccine. The studies outlined in this proposal will provide important insight toward achieving that goal.