Zhu Shanli, Feng Yan, Rao Pinhuan, Xue Xiangyang, Chen Shao, Li Wenshu, Zhu Guanbao, Zhang Lifang
Department of Microbiology and Immunology, Wenzhou Medical University, Wenzhou, 325000, China,
Appl Microbiol Biotechnol. 2014 May;98(9):4107-17. doi: 10.1007/s00253-014-5517-x. Epub 2014 Jan 24.
Chlamydia trachomatis is the leading cause of sexually transmitted infections worldwide. There is currently no commercially available vaccine against C. trachomatis. Major outer membrane protein (MOMP) of C. trachomatis is considered to be an ideal candidate for prophylactic vaccine. We designed a MOMP multi-epitope containing T- and B-cell epitope-rich peptides and developed hepatitis B surface antigen (HBsAg) as antigen delivery vehicle. In order to study the immunogenicity and efficacy of the candidate vaccine in a murine model of chlamydial genital infection, we engineered a recombinant plasmid expressing HBsAg and MOMP multi-epitope genes. Results of reverse transcription polymerase chain reaction and immunofluorescence assay revealed successful expression of the recombinant HBsAg/MOMP multi-epitope gene at both the transcription and translation levels. Intramuscular administration in mice was able to elicit not only antibodies against Chlamydia and HBsAg but also cytotoxic T lymphocyte activity against Chlamydia. In addition, mice inoculated with the rHBsAg were highly resistant to C. trachomatis genital infection. The rHBsAg DNA with MOMP multi-epitope appended at the C terminus of the HBsAg stimulated a stronger immune response and protective response than that appended at the N terminus. Together, our results suggested that use of a recombinant HBsAg encoding the MOMP multi-epitope could be a powerful approach to developing a safe and immunogenic C. trachomatis vaccine.
沙眼衣原体是全球性传播感染的主要病因。目前尚无针对沙眼衣原体的商业化疫苗。沙眼衣原体的主要外膜蛋白（MOMP）被认为是预防性疫苗的理想候选物。我们设计了一种包含富含T细胞和B细胞表位的肽段的MOMP多表位，并开发了乙肝表面抗原（HBsAg）作为抗原递送载体。为了在衣原体性生殖器感染的小鼠模型中研究候选疫苗的免疫原性和效力，我们构建了一种表达HBsAg和MOMP多表位基因的重组质粒。逆转录聚合酶链反应和免疫荧光分析结果显示，重组HBsAg/MOMP多表位基因在转录和翻译水平均成功表达。对小鼠进行肌肉注射不仅能够引发针对衣原体和HBsAg的抗体，还能引发针对衣原体的细胞毒性T淋巴细胞活性。此外，接种rHBsAg的小鼠对沙眼衣原体性生殖器感染具有高度抗性。在HBsAg的C末端附加MOMP多表位的rHBsAg DNA比在N末端附加时刺激产生更强的免疫反应和保护反应。总之，我们的结果表明，使用编码MOMP多表位的重组HBsAg可能是开发安全且具有免疫原性的沙眼衣原体疫苗的有效方法。
