Xu Wei, Chu Yiwei, Zhang Ruihua, Xu Huanbin, Wang Ying, Xiong Sidong
Department of Immunology, Shanghai Medical College of Fudan University, Shanghai, PR China.
Virology. 2005 Apr 10;334(2):255-63. doi: 10.1016/j.virol.2005.01.040.
CD8(+) T cells play a critical role in protective immunity against Hepatitis B Virus (HBV). Epitope-based DNA vaccines expressing HBV-dominant CTL epitopes can be used as candidate vaccines capable of inducing cytotoxic T Lymphocytes (CTL) responses. A plasmid DNA encoding a CTL epitope of HBV core antigen, HBc(18-27), was constructed. Intramuscular immunization of C57BL/6 mice with this DNA vaccine resulted in successful induction of HBV-specific CTL responses. In order to promote transportation of the peptide into endoplasmic reticulum (ER) to bind to MHC class I molecules for optimal class I antigen presentation, an ER targeting sequence (ERTS) was fused with the C(18-27) encoding gene. ERTS fusion significantly enhanced specific CD8(+) T cell responses in terms of CTL cytolysis as well as IFN-gamma secretion. This enhancement was correlated with promoted epitope presentation on target cell surface. We report here an enhanced immunogenicity of an epitope-based DNA vaccine using an ER targeting signal sequence, which has significant implications for future design of therapeutic HBV vaccine.
CD8(+) T细胞在抗乙型肝炎病毒（HBV）的保护性免疫中发挥关键作用。表达HBV优势CTL表位的基于表位的DNA疫苗可作为能够诱导细胞毒性T淋巴细胞（CTL）反应的候选疫苗。构建了一种编码HBV核心抗原CTL表位HBc(18 - 27)的质粒DNA。用这种DNA疫苗对C57BL/6小鼠进行肌肉内免疫成功诱导了HBV特异性CTL反应。为了促进肽转运到内质网（ER）以与MHC I类分子结合从而实现最佳的I类抗原呈递，将内质网靶向序列（ERTS）与编码C(18 - 27)的基因融合。ERTS融合在CTL细胞溶解以及IFN-γ分泌方面显著增强了特异性CD8(+) T细胞反应。这种增强与靶细胞表面表位呈递的促进相关。我们在此报告使用内质网靶向信号序列增强了基于表位的DNA疫苗的免疫原性，这对治疗性HBV疫苗的未来设计具有重要意义。
