title: A novel mouse model for immunogenic evaluation of human HBV vaccines.
abstract: To prepare a human HBV vaccine, investigators need an animal model that can help them screen and prioritize vaccine candidates. In this study, HBV/HLA-A2.1 double transgenic mice (dTg), confirmed by analysis of genomic integration and by observation of long-term expression of HBV and HLA genes, were generated for the first time. The HBV/HLA-A2.1 dTg not only display tolerance to HBV antigens (Ags), but also have the ability to process and present HLA-A2 restricted antigenic epitopes. The animals vaccinated with HLA-A2 restricted HBc(18-27) or HBs(183-191) epitope peptide vaccine induced effective HLA-A2 restricted peptide-specific cytolytic T lymphocyte responses. This was supported by the evidence of cytotoxicity assay, ELISPOT and tetramer staining analysis. Furthermore, T cell tolerance against HBV Ags in HBV/HLA-A2.1 dTg was broken by the HBc(18-27) or HBs(183-191) peptide vaccine. In conclusion, HBV/HLA-A2.1 dTg was demonstrated to be useful model for in vivo immunogenicity testing of human HBV-based vaccines.
authors.affiliation: Department of Medical Genetics, The Second Military Medical University, Yangpu District, 200433 Shanghai, China.
authors.forename: Yingjun
authors.initials: Y
authors.lastname: Guo
authors.forename: Ding
authors.initials: D
authors.lastname: Ren
authors.forename: Xiaowen
authors.initials: X
authors.lastname: He
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.forename: Shuxia
authors.initials: S
authors.lastname: Song
authors.forename: Ying
authors.initials: Y
authors.lastname: He
authors.forename: Shuhan
authors.initials: S
authors.lastname: Sun
mesh_terms: D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D015789:HLA-A2 Antigen / Q000235:genetics; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D017918:Orthohepadnavirus / Q000235:genetics / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000939:Epitopes; D015789:HLA-A2 Antigen; D017325:Hepatitis B Vaccines; D022223:Vaccines, Subunit