title: Vaccination with a fusion DNA vaccine encoding hepatitis B surface antigen fused to the extracellular domain of CTLA4 enhances HBV-specific immune responses in mice: implication of its potential use as a therapeutic vaccine.
abstract: Fusion of specific antigens to extracellular domain of cytotoxic-T-lymphocyte-associated antigen 4 (CTLA4) represents a promising approach to increase the immunogenicity of DNA vaccines. We evaluated this interesting approach for its enhancement on HBV-specific immune responses and its antiviral effects in HBV transgenic mice. A fusion plasmid encoding the extracellular domain of CTLA4 linked with HBsAg was constructed. Mice were immunized by this fusion plasmid. Vaccination with the CTLA4-fused DNA not only induced much higher level of anti-HBs antibody, but also increased HBsAg-specific CD8+ response as well as CTL response in BALB/c mice. Furthermore, both Th1 and Th2 responses were augmented. In HBV transgenic mice, the levels of circulating HBsAg and HBV DNA replication were down-regulated by induction of higher anti-HBs antibody and HBsAg-specific CD8+ response after vaccination with the fusion plasmid. Thus, the CTLA4-fused DNA vaccine led to breakdown of immune tolerance to viral infection in HBV transgenic mice, which might be used as a therapeutic vaccine in HBV infection.
authors.affiliation: State Key Laboratory of Infectious Disease Diagnosis and Treatment, First Affiliated Hospital of Zhejiang University, Qingchun Road 79, Hangzhou 310003, China. zchen_2010@hotmail.com
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhou
authors.forename: Guoping
authors.initials: G
authors.lastname: Peng
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Jin
authors.forename: Jie
authors.initials: J
authors.lastname: Tang
authors.forename: Zhi
authors.initials: Z
authors.lastname: Chen
mesh_terms: D056704:Adaptive Immunity / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood / Q000276:immunology; D015703:Antigens, CD / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D019556:COS Cells; D060908:CTLA-4 Antigen; D002522:Chlorocebus aethiops; D003601:Cytotoxicity Tests, Immunologic; D004279:DNA, Viral / Q000097:blood; D005260:Female; D015870:Gene Expression; D005822:Genetic Vectors / Q000235:genetics; D006514:Hepatitis B Surface Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology*; D006515:Hepatitis B virus / Q000235:genetics / Q000276:immunology*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000276:immunology / Q000628:therapy* / Q000821:virology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D017434:Protein Structure, Tertiary / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014162:Transfection; D014611:Vaccination; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology* / Q000627:therapeutic use*
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D007074:Immunoglobulin G; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D015847:Interleukin-4; D007371:Interferon-gamma