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Stem Cell-Derived Viral Ag-Specific T Lymphocytes Suppress HBV Replication in Mice
Published on: September 25, 2019
Dendritic cell-based vaccination with lentiviral vectors encoding ubiquitinated hepatitis B core antigen enhances
Shenglan Dai1, Meng Zhuo1, Linlin Song1
1Department of Infectious Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
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.
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