Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections.
J Infect Dis
; 223(1): 128-138, 2021 01 04.
Article
em En
| MEDLINE
| ID: mdl-31994701
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.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Vírus Delta da Hepatite
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Vírus da Hepatite B
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Hepatite B Crônica
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Hepatite D Crônica
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Internalização do Vírus
Limite:
Animals
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Female
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Humans
Idioma:
En
Revista:
J Infect Dis
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Suécia