MOLECULAR CHLAMYDIAL VACCINE DEVELOPMENT

本项目的目标是发展亚单位或重组 预防沙眼衣原体感染的疫苗。衣原体 是性传播疾病和沙眼的主要原因 它仍然是世界上可预防失明的主要原因。一个 预防衣原体感染或减少衣原体感染的疫苗 疾病后遗症是非常需要的。衣原体感染仅限于 眼球生殖器粘膜，由多个衣原体血清型引起。 局部抗体(SIgA)在免疫保护中起着重要作用 黏膜上皮细胞的衣原体定植和感染。这个 这项工作的目标是产生一个亚单位或重组衣原体 一种能激发广泛交叉保护性抗衣原体的疫苗 在眼球粘膜中和。为了达到这个目的，我们有 确定衣原体的关键T辅助细胞和B细胞中和表位 主要外膜蛋白(MOMP)；中和抗原的原理 衣原体。正在使用几种方法来针对这些关键的MOMP 抗原决定簇，以引起粘膜免疫反应。这些措施包括 将表位作为化学和基因融合与B 霍乱毒素亚单位与重组脊髓灰质炎病毒的构建 表达MOMP表位作为与脊髓灰质炎病毒主要衣壳的融合基因 蛋白质VP1。我们最有希望的结果是重组 脊髓灰质炎病毒载体。表达抗原性的重组脊髓灰质炎病毒 常见的MOMP中和表位的增长几乎与亲本病毒和 在产生高滴度血清的兔中具有高度的免疫原性 在体外广泛交叉中和的衣原体抗体。 未来的工作将包括评估 脊髓灰质炎病毒/MOMP嵌合病毒在非人类灵长类动物模型中的C. 沙眼和生殖道感染。

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.