{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:36:26Z","timestamp":1790753786135,"version":"4.1.0"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,7,31]],"date-time":"2021-07-31T00:00:00Z","timestamp":1627689600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["TRR179, TP18"],"award-info":[{"award-number":["TRR179, TP18"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010661","name":"Horizon 2020 Framework Programme","doi-asserted-by":"publisher","award":["TherVacB Consortium"],"award-info":[{"award-number":["TherVacB Consortium"]}],"id":[{"id":"10.13039\/100010661","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009318","name":"Helmholtz Association","doi-asserted-by":"publisher","award":["PoC Initiative"],"award-info":[{"award-number":["PoC Initiative"]}],"id":[{"id":"10.13039\/501100009318","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>During the natural course of chronic hepatitis B virus (HBV) infection, the hepatitis B e antigen (HBeAg) is typically lost, while the direct transmission of HBeAg-negative HBV may result in fulminant hepatitis B. While the induction of HBV-specific immune responses by therapeutic vaccination is a promising, novel treatment option for chronic hepatitis B, it remains unclear whether a loss of HBeAg may influence its efficacy or tolerability. We therefore generated an adeno-associated virus (AAV)-vector that carries a 1.3-fold overlength HBV genome with a typical stop-codon mutation in the pre-core region and initiates the replication of HBeAg(\u2212) HBV in mouse livers. Infection of C57BL\/6 mice established persistent HBeAg(\u2212) HBV-replication without any detectable anti-HBV immunity or liver damage. HBV-carrier mice were immunized with TherVacB, a therapeutic hepatitis B vaccine that uses a particulate HBV S and a core protein for prime vaccination, and a modified vaccinia Ankara (MVA) for boost vaccination. The TherVacB immunization of HBeAg(+) and HBeAg(\u2212) HBV carrier mice resulted in the effective induction of HBV-specific antibodies and the loss of HBsAg but only mild liver damage. Intrahepatic, HBV-specific CD8 T cells induced in HBeAg(\u2212) mice expressed more IFN\u03b3 but showed similar cytolytic activity. This indicates that the loss of HBeAg improves the performance of therapeutic vaccination by enhancing non-cytolytic effector functions.<\/jats:p>","DOI":"10.3390\/vaccines9080841","type":"journal-article","created":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T21:46:44Z","timestamp":1627854404000},"page":"841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Immunogenicity and Antiviral Response of Therapeutic Hepatitis B Vaccination in a Mouse Model of HBeAg-Negative, Persistent HBV Infection"],"prefix":"10.3390","volume":"9","author":[{"given":"Anna D.","family":"Kosinska","sequence":"first","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, D-81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Partner Site, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6159-8286","authenticated-orcid":false,"given":"Julia","family":"Festag","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"M\u00fcck-H\u00e4usl","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1294-8336","authenticated-orcid":false,"given":"Marvin M.","family":"Festag","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theresa","family":"Asen","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-1911","authenticated-orcid":false,"given":"Ulrike","family":"Protzer","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, D-81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Partner Site, D-81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,31]]},"reference":[{"key":"ref_1","unstructured":"(2021, March 10). 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