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Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections

(2021) JOURNAL OF INFECTIOUS DISEASES. 223(1). p.128-138
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Abstract
Background. 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.
Keywords
chronic hepatitis B, immunotherapy, PreS1 antibodies, T-cell tolerance, hepatitis D antigen, UPA-SCID MOUSE, IMMUNE TOLERANCE, C VIRUS, HUMANIZED ANTIBODY, SURFACE-ANTIGEN, HUMAN LIVER, T-CELLS, HBV, DNA, PROTEIN

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MLA
Maravelia, P., et al. “Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections.” JOURNAL OF INFECTIOUS DISEASES, vol. 223, no. 1, 2021, pp. 128–38, doi:10.1093/infdis/jiaa036.
APA
Maravelia, P., Frelin, L., Ni, Y., Pérez, N., Ahlén, G., Jagya, N., … Sällberg, M. (2021). Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections. JOURNAL OF INFECTIOUS DISEASES, 223(1), 128–138. https://doi.org/10.1093/infdis/jiaa036
Chicago author-date
Maravelia, P, L Frelin, Y Ni, NC Pérez, G Ahlén, N Jagya, G Verch, et al. 2021. “Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections.” JOURNAL OF INFECTIOUS DISEASES 223 (1): 128–38. https://doi.org/10.1093/infdis/jiaa036.
Chicago author-date (all authors)
Maravelia, P, L Frelin, Y Ni, NC Pérez, G Ahlén, N Jagya, G Verch, Lieven Verhoye, L Pater, M Johansson, A Pasetto, Philip Meuleman, S Urban, and M Sällberg. 2021. “Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections.” JOURNAL OF INFECTIOUS DISEASES 223 (1): 128–138. doi:10.1093/infdis/jiaa036.
Vancouver
1.
Maravelia P, Frelin L, Ni Y, Pérez N, Ahlén G, Jagya N, et al. Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections. JOURNAL OF INFECTIOUS DISEASES. 2021;223(1):128–38.
IEEE
[1]
P. Maravelia et al., “Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections,” JOURNAL OF INFECTIOUS DISEASES, vol. 223, no. 1, pp. 128–138, 2021.
@article{8654099,
  abstract     = {{Background. 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.}},
  author       = {{Maravelia, P and Frelin, L and Ni, Y and Pérez, NC and Ahlén, G and Jagya, N and Verch, G and Verhoye, Lieven and Pater, L and Johansson, M and Pasetto, A and Meuleman, Philip and Urban, S and Sällberg, M}},
  issn         = {{0022-1899}},
  journal      = {{JOURNAL OF INFECTIOUS DISEASES}},
  keywords     = {{chronic hepatitis B,immunotherapy,PreS1 antibodies,T-cell tolerance,hepatitis D antigen,UPA-SCID MOUSE,IMMUNE TOLERANCE,C VIRUS,HUMANIZED ANTIBODY,SURFACE-ANTIGEN,HUMAN LIVER,T-CELLS,HBV,DNA,PROTEIN}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{128--138}},
  title        = {{Blocking entry of hepatitis B and D viruses to hepatocytes as a novel immunotherapy for treating chronic infections}},
  url          = {{http://dx.doi.org/10.1093/infdis/jiaa036}},
  volume       = {{223}},
  year         = {{2021}},
}

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