NEUTRALIZABLE EPITOPES OF CHLAMYDIA TRACHOMATIS

这项提案的总体目标是确定肽是否 对应于主要外膜的可中和的连续表位 沙眼衣原体膜蛋白（MOMP）能够赋予 防止感染这种微生物。这种病原体是 西方世界性传播疾病的主要原因， 被认为是导致不孕的主要因素。也是 这是不发达国家可预防失明的主要原因。 由于与该生物体相关的发病率， 用来接种完整的生物体 从疫苗试验来看， 得出的结论是，宿主的免疫反应导致了 与衣原体感染有关的后遗症。 最近，在一个 努力避免超敏反应以及 增加疫苗、亚单位疫苗中的血清型数量 已经被提出作为一种可能的解决方案。尽管我们意识到 保护性B和T细胞表位最终需要被并入 在这个建议中，我们将重点放在表位上， 我们已经确定并定性为毗连和中立， 确定代表这些表位的肽是否能够提供 保护宿主。我们将首先关注血清型E，因为它是 最常见的C. 沙眼 肽代表 可中和表位将单独、组合和作为 共线性肽构建体，其引发保护性免疫的能力 反应 共线性肽将用于建立最佳的 肽构建、免疫途径、剂量、递送系统和如果 必要的，佐剂，将引起强烈的粘膜反应。 为了完成这些工作，我们将使用一种小鼠模型， 衣原体生殖器感染，以建立可重复的模型 这将适合于测试免疫的能力， 用肽构建体建立的参数，以保护或减弱 衣原体感染和不孕症的后遗症 信息 从这种方法中获得的好处应该会使我们更接近于回答这个问题， 关于中和抗体在衣原体感染中的作用。

The overall goal of this proposal is to determine whether peptides corresponding to neutralizable contiguous epitopes of the major outer membrane protein (MOMP) of Chlamydia trachomatis are able to confer protection from an infection with this organism. This pathogen is the leading cause of sexually transmitted disease in the Western world and has been implicated as a major contributing factor to infertility. It is also the leading cause of preventable blindness in underdeveloped countries. Due to the morbidity associated with this organism, attempts have been made to vaccinate with the intact organism. From vaccine trials it was concluded that the host immune response contributed to the damaging sequelae associated with a chlamydial infection. More recently in an effort to both circumvent the hypersensitivity reaction as well as increase the number of serovars represented in a vaccine, subunit vaccines have been proposed as a possible solution. Although we realize that both protective B and T cell epitopes will eventually need to be incorporated into an effective vaccine, in this proposal we will focus on epitopes that we have identified and characterized as contiguous and neutralizable to determine whether peptides representing these epitopes can afford protection to the host. We will first focus on serovar E since it is the most common genital isolate of C. trachomatis. Peptides representing neutralizable epitopes will be tested alone, in combination and as a colinear peptide construct for their ability to elicit a protective immune response. The colinear peptides will be used to establish the optimal peptide construction, immunization route, dose, delivery system and if necessary, adjuvant that will elicit a strong mucosal response. Paralleling these efforts we will be working with a murine model of a chlamydial genital infection in order to establish a reproducible model that will be suitable for testing the ability of the immunization parameters established with the peptide constructs to protect or attenuate from a chlamydial infection and the sequelae of infertility. Information gained from this approach should bring us closer to answering the question as to the role of neutralizing antibodies in chlamydial infections.