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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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>We here describe a novel immunotherapy for chronic HBV\/HDV that targets viral entry to complement NAs and coming therapies inhibiting viral maturation.<\/jats:p><\/jats:sec>","DOI":"10.1093\/infdis\/jiaa036","type":"journal-article","created":{"date-parts":[[2020,1,25]],"date-time":"2020-01-25T12:11:08Z","timestamp":1579954268000},"page":"128-138","source":"Crossref","is-referenced-by-count":16,"title":["Blocking Entry of Hepatitis B and D Viruses to Hepatocytes as a Novel Immunotherapy for Treating Chronic Infections"],"prefix":"10.1093","volume":"223","author":[{"given":"Panagiota","family":"Maravelia","sequence":"first","affiliation":[{"name":"Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Stockholm, 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