title: Dendritic cell-based vaccination with lentiviral vectors encoding ubiquitinated hepatitis B core antigen enhances hepatitis B virus-specific immune responses in vivo.
abstract: The activity of hepatitis B virus (HBV)-specific cytotoxic T lymphocytes (CTLs) plays a predominant role in the clearance of HBV. Dendritic cells (DCs) are key antigen-presenting cells and play an important role in the initiation of immune responses. We previously verified that lentiviral vector encoding ubiquitinated hepatitis B core antigen (LV-Ub-HBcAg) effectively transduced DCs to induce maturation, and the mature DCs efficiently induced T cell polarization to Th1 and generated HBcAg-specific CTLs ex vivo. In this study, HBV-specific immune responses of LV-Ub-HBcAg in BALB/c mice (H-2Kd) were evaluated. It was shown that direct injection of LV-Ub-HBcAg increased the production of cytokines IL-2 and IFN-γ, elicited strong antibody responses, and remarkably generated a high percentage of IFN-γ+CD8+ T cells with HBV-specific CTL responses in BALB/c mice. In addition, direct injection of LV-Ub-HBcAg induced potent anti-HBV immune responses, similar to those elicited by in vitro-transduced DCs. In conclusion, the DC-based therapeutic vaccine LV-Ub-HBcAg elicited specific antibody immune responses and induced robust specific CTL activity in vivo.
authors.affiliation: Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Shenglan
authors.initials: S
authors.lastname: Dai
authors.affiliation: Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Meng
authors.initials: M
authors.lastname: Zhuo
authors.affiliation: Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Linlin
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China tzhhao@163.com zangguoqin@126.com.
authors.forename: Zhenghao
authors.initials: Z
authors.lastname: Tang
authors.affiliation: Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China tzhhao@163.com zangguoqin@126.com.
authors.forename: Guoqing
authors.initials: G
authors.lastname: Zang
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000276:immunology*; D005822:Genetic Vectors / Q000008:administration & dosage; D006512:Hepatitis B Core Antigens / Q000737:chemistry* / Q000235:genetics / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000235:genetics / Q000276:immunology*; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D006512:Hepatitis B Core Antigens; D017325:Hepatitis B Vaccines
keywords: cytotoxic T lymphocyte; dendritic cell (DC); hepatitis B virus (HBV); lentiviral vector (LV); ubiquitin