MOLECULAR CHLAMYDIAL VACCINE DEVELOPMENT

沙眼衣原体是性传播疾病的主要原因， 世界范围内没有有效疫苗的疾病。 的 该项目的目标是设计重组疫苗， 预防沙眼衣原体感染。 衣原体 感染仅限于眼生殖粘膜， 多种衣原体血清型。局部抗体（sIgA）被认为是 在防止衣原体定植方面发挥重要作用， 粘膜上皮细胞感染。 这项工作的目标是 产生亚单位或重组衣原体疫苗， 广泛交叉保护性抗衣原体中和伊加抗体. 眼生殖粘膜 衣原体主要外膜蛋白 （MOMP）是衣原体表面上的主要中和抗原。 有几种方法被用于靶向rMOMP或保护性MOMP 表位以引起sIgA抗衣原体中和抗体。 这些 包括将表位作为与B亚基的基因融合物掺入 大肠大肠杆菌肠毒素（LT），重组大肠杆菌LT 表达MOMP表位作为与脊髓灰质炎病毒的基因融合物的脊髓灰质炎病毒 主要衣壳蛋白VP 1和MOMP包封到微球中。 我们的研究结果表明，这些方法中的每一种都能够引发 高滴度血清抗衣原体中和抗体（IgG） 然而，在肠胃外免疫之后，这些系统中没有一个被 有效地引起局部sIgA反应。 未来的研究将集中在 重组LT-MOMP免疫原的产生， 优化LT的粘膜佐剂性和粘膜免疫应答 反对MOMP。

Chlamydial trachomatis is a leading cause of sexually transmitted diseases worldwide for which there is no effective vaccine. The objective of this project is the design of recombinant vaccines for the prevention of infections caused by Chlamydia trachomatis. Chlamydial infections are restricted to the oculogenital mucosae and are caused by multiple chlamydial serovars. Local antibody (sIgA) is thought to play 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 IgA antibodies at the oculogenital mucosae. The chlamydial major outer membrane protein (MOMP) is the principle neutralizing antigen on the chlamydial surface. Several approaches are being used to target rMOMP or protective MOMP epitopes to evoke sIgA anti-chlamydial neutralizing antibodies. These include incorporation of the epitopes as gene fusions with the B subunit of E. coli enterotoxin (LT), the construction of recombinant polioviruses expressing MOMP epitopes as gene fusions with the poliovirus major capsid protein VP1, and encapsulation of MOMP into microspheres. Our findings show that each of these approaches is capable of eliciting high titered serum anti-chlamydial neutralizing antibodies (IgG) following parenteral immunization however none of these systems has been effective in evoking local sIgA responses. Future studies will focus on the generation of recombinant LT-MOMP immunogens designed to both optimize the mucosal adjuvanticity of LT and the mucosal immune response against the MOMP.