MOLECULAR CHLAMYDIAL VACCINE DEVELOPMENT

本项目的目标是开发亚单位或重组 预防沙眼衣原体感染的疫苗。 衣原体 是性传播疾病（STD）和沙眼的主要原因 这仍然是世界上可预防失明的主要原因。 一 预防衣原体感染或减少衣原体感染的疫苗 疾病后遗症是急需的。 衣原体感染仅限于 眼生殖器粘膜，由多种衣原体血清型引起。 局部抗体（sIgA）在保护机体免受 衣原体定植和粘膜上皮细胞感染。 的 这项工作的目标是产生亚单位或重组衣原体 能引起广泛交叉保护性抗衣原体的疫苗 中和眼生殖器粘膜。 为此，我们 确定了衣原体的关键T辅助细胞和B细胞中和表位， 主要外膜蛋白（MOMP）; 披衣目前正在采用几种方法来针对这些关键的MOMP 抗原决定簇以引起粘膜免疫应答。 这些包括 将表位作为化学和基因融合物与B结合 霍乱毒素亚单位及重组脊髓灰质炎病毒的构建 将MOMP表位表达为与脊髓灰质炎病毒主要衣壳的基因融合物 VP 1蛋白。 我们最有希望的结果是重组 脊髓灰质炎病毒载体。 抗原性表达的重组脊髓灰质炎病毒 常见MOMP中和表位的生长几乎与亲本病毒一样好， 在家兔体内具有高度免疫原性， 体外广泛交叉中和的衣原体抗体。 未来的工作将涉及评估的保护效力， 脊髓灰质炎病毒/MOMP嵌合病毒在C. 沙眼眼和生殖道感染。

The objective of this project is the development of subunit or recombinant vaccine to prevent infections caused by Chlamydia trachomatis. Chlamydiae are a major cause of sexually transmitted diseases (STDs) and trachoma which remains the worlds leading cause Of preventable blindness. A vaccine capable of preventing chlamydial infection or reducing chlamydial disease sequelae is badly needed. Chlamydial infections are restricted to the oculogenital mucosae and are caused by multiple chlamydial serovars. Local antibody (sIgA) plays an important role in protection against chlamydial colonization and infection of mucosal epithelial cells. The goal of this work is to generate a subunit or recombinant chlamydial vaccine capable of evoking broadly cross-protective anti-chlamydial neutralizing at the oculagenital mucosae. Towards this end we have identified key T-helper and B-cell neutralizing epitopes of the chlamydial major outer membrane protein (MOMP); the principle neutralizing antigen of chlamydiae. Several approaches are being used to target these key MOMP antigenic determinants to evoke a mucosal immune response. These include incorporation of the epitopes as chemical and gene fusions with the B subunit of cholera toxin and the construction of recombinant polioviruses expressing MOMP epitopes as gene fusions with the poliovirus major capsid protein VP1. Our most promising results have been with recombinant poliovirus vectors. Recombinant poliovirus expressing antigenically common MOMP neutralizing epitopes grew nearly as well as parent virus and were highly immunogenic in rabbits evoking high titered serum anti- chlamydial antibodies that were broadly cross neutralizing in vitro. Future work will involve evaluating the protective efficacy of the poliovirus/MOMP chimeric virus in a non-human primate animal model of C. trachomatis ocular and genital tract infection.