Therapeutic Vaccination with Lentiviral Vector in HBV-Persistent Mice and Two Inactive HBsAg Carriers
Time:2023-10-10
Authors: Yumeng Zhang, Maryline Bourgine, Yanmin Wan, Jieyu Song, Zongying Li, Yiqi Yu, Wangfang Jiang, Mingzhe Zhou, Cuiyuan Guo, Didier Santucci, Xiao Liang, Christian Brechot, Wenhong Zhang, Pierre Charneau, Hong Wu, Chao Qiu
Abstract:
Background & Aims: Immunotherapy for chronic hepatitis B virus (HBV) infection has not yet demonstrated sufficient efficacy. We developed a non-integrative lentiviral-vectored therapeutic vaccine for chronic hepatitis B and tested its anti-viral effects in HBV-persistent mice and two inactive HBsAg carrier patients.
Methods: Lentiviral vectors (LV) encoding core, preS1, or large HBs (LHBs) proteins of HBV were evaluated for immunogenicity in HBV-naïve mice and therapeutic efficacy in a murine model of chronic HBV infection. In addition, two inactive HBsAg carrier patients each received two doses of 5×107 TU or 1×108 TU lentiviral-vectored LHBs (LV-LHBs), respectively. The endpoints were safety, LHBs-specific T cell response, and serum HBsAg levels during a 24-week of follow-up.
Results: In the mouse models, LV-LHBs was the most promising in eliciting robust antigen-specific T cells and in reducing the levels of serum HBsAg and viral load. By the end of the 34-week observation period, six out of 10 (60%) HBV-persistent mice vaccinated with LV-LHBs achieved serum HBsAg loss and significant depletion of HBV-positive hepatocytes in the liver. In the two inactive HBsAg carrier patients, vaccination with LV-LHBs induced a considerable increase in the number of peripheral LHBs-specific T cells in one patient, and a weak but detectable response in the other, accompanied by a sustained reduction of HBsAg (-0.31 log10 IU/ml and -0.46 log10 IU/ml, respectively) from baseline to nadir.
Conclusions: A lentiviral-vectored therapeutic vaccine for chronic HBV infection demonstrated the potential to improve HBV-specific T cell response and deplete HBV-positive hepatocytes, leading to a sustained loss or reduction of serum HBsAg.
Keywords:Chronic hepatitis B, Immunotherapy, Lentiviral-vectored vaccine, Immunotolerance
Download from: https://doi.org/10.1016/j.jhep.2023.09.019
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