Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections
Panagiota Maravelia, Lars Frelin, Yi Ni, Noelia Caro Pérez, Gustaf Ahlén, Neetu Jagya, Georg Verch, Lieven Verhoye, Lena Pater, Magnus Johansson, Anna Pasetto, Philip Meuleman, Stephan Urban, Matti Sällberg
The Journal of Infectious Diseases, Volume 223, Issue 1, 1 January 2021, Pages 128–138, https://doi.org/10.1093/infdis/jiaa036
Published:
29 January 2020
Article history
Chronic hepatitis B and D virus (HBV/HDV) infections can cause cancer. Current HBV therapy using nucleoside analogues (NAs) is life-long and reduces but does not eliminate the risk of cancer. A hallmark of chronic hepatitis B is a dysfunctional HBV-specific T-cell response. We therefore designed an immunotherapy driven by naive healthy T cells specific for the HDV antigen (HDAg) to bypass the need for HBV-specific T cells in order to prime PreS1-specific T cells and PreS1 antibodies blocking HBV entry.
Methods
Ten combinations of PreS1 and/or HDAg sequences were evaluated for induction of PreS1 antibodies and HBV- and HDV-specific T cells in vitro and in vivo. Neutralization of HBV by PreS1-specific murine and rabbit antibodies was evaluated in cell culture, and rabbit anti-PreS1 were tested for neutralization of HBV in mice repopulated with human hepatocytes.
Results
The best vaccine candidate induced T cells to PreS1 and HDAg, and PreS1 antibodies blocking HBV entry in vitro. Importantly, adoptive transfer of PreS1 antibodies prevented, or modulated, HBV infection after a subsequent challenge in humanized mice.
Conclusions
We here describe a novel immunotherapy for chronic HBV/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation.
chronic hepatitis B, immunotherapy, PreS1 antibodies, T-cell tolerance, hepatitis D antigen作者: StephenW 时间: 2021-1-9 20:48