NEUTRALIZABLE EPITOPES OF CHLAMYDIA TRACHOMATIS

这项提案的总体目标是确定多肽是否 对应于主要外部的可中和的连续表位 沙眼衣原体膜蛋白(MOMP)可提供 保护免受这种微生物的感染。这种病原体是 西方世界性传播疾病的主要原因，并已 被认为是导致不孕不育的主要因素。它也是 是不发达国家可预防失明的主要原因。 由于与这种生物相关的发病率，已经尝试 用完整的有机体接种疫苗。从疫苗试验来看， 结论是宿主的免疫反应导致了损害 与衣原体感染相关的后遗症。最近在一个 努力避免过敏反应以及 增加疫苗、亚单位疫苗中代表的血清型数量 已经被提出作为一种可能的解决方案。尽管我们意识到两者 保护性的B和T细胞表位最终将需要合并 成为一种有效的疫苗，在这项提议中，我们将重点放在 我们已经确定并描述为连续的和可中和的 确定代表这些表位的肽是否能够负担得起 对宿主的保护。我们将首先关注E血清型，因为它是 沙眼衣原体最常见的生殖器分离株。代表多肽的 中和表位将单独、组合和作为 共线多肽的构建及其诱导保护性免疫的能力 回应。共线肽将被用于建立最优的 多肽结构、免疫途径、剂量、递送系统和IF 必要的佐剂，会引起强烈的粘膜反应。 在这些努力的同时，我们将用一种小鼠模型来研究 建立可复制的衣原体生殖道感染模型 这将适合于测试免疫的能力 利用多肽结构建立的参数以保护或衰减 来自衣原体感染和不孕不育的后遗症。信息 从这种方法中获得的收益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.