Immunity to Chlamydial Genital Infection

描述(申请人提供)：沙眼衣原体性传播感染在世界范围内造成相当大的发病率和社会经济负担，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。衣原体泌尿生殖道感染很容易用抗生素治愈，但仅基于抗菌化疗的控制措施因无症状感染的频率和延误诊断而受到阻碍。通过开发一种安全有效的疫苗，有可能彻底控制沙眼衣原体的性传播疾病。在过去的十年里，通过使用衣原体感染的小鼠模型进行的研究，人们对衣原体生殖道感染的保护性免疫有了更高的理解。从利用小鼠感染模型进行的研究中获得的见解令人相当感兴趣，因为它们为开发有效的疫苗提供了希望。利用衣原体生殖道感染的小鼠模型，我们发现抗衣原体抗体在生殖道再感染过程中对动物有明显的保护作用。在我们提出的研究中，我们将通过4个特定的目标进一步定义和表征保护性抗体介导的反应。目的1专注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；目标2使用免疫组学方法来鉴定保护性康复血清识别的衣原体抗原；在目标3中，我们将测试目标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鉴定的细胞群体，在目标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。只有开发一种有效的疫苗，才能持续控制衣原体泌尿生殖道感染。本提案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.