Endoplasmic reticulum targeting sequence enhances HBV-specific cytotoxic T lymphocytes induced by a CTL epitope-based DNA vaccine.
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.
Xu
Wei
W
Department of Immunology, Shanghai Medical College of Fudan University, Shanghai, PR China.
Chu
Yiwei
Y
Zhang
Ruihua
R
Xu
Huanbin
H
Wang
Ying
Y
Xiong
Sidong
S
D000818:Animals; D003602:Cytotoxicity, Immunologic; D004721:Endoplasmic Reticulum / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D006509:Hepatitis B / Q000517:prevention & control; D006512:Hepatitis B Core Antigens / Q000235:genetics / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D018984:Epitopes, T-Lymphocyte; D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines; D019444:Vaccines, DNA; D007371:Interferon-gamma