{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T20:01:10Z","timestamp":1778702470325,"version":"3.51.4"},"reference-count":59,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T00:00:00Z","timestamp":1773619200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"German Research Foundation","doi-asserted-by":"publisher","award":["272983813"],"award-info":[{"award-number":["272983813"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EU Horizon 2020 consortium TherVacB"},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"crossref"}]},{"name":"German Ministry for Research, Technology, and Space"},{"name":"DZIF Academy"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/Objectives: Eliciting robust immune responses against the hepatitis B virus (HBV) through therapeutic vaccination holds promise for curing chronic hepatitis B. We previously developed the heterologous protein prime\/viral vector boost clinical vaccine candidate, TherVacB. Here, we evaluated a replication-competent chimeric vesicular stomatitis virus vector (VSV-GP) as an alternative viral vector boost vaccine. Methods: A recombinant VSV-GP vector co-expressing HBV surface and core antigens (VSV-GP-HBs\/c) was generated and characterized for antigen expression. Its immunogenicity, antiviral efficacy, and durability were assessed in HBV-na\u00efve and HBV-carrier mice, using protein primed, viral vector-primed, and multi-viral vector boost regimens. Results: VSV-GP-HBs\/c efficiently expressed both HBV antigens in vitro. A single immunization with VSV-GP-HBs\/c induced only weak HBV-specific immune responses in vivo. Replacing protein priming with VSV-GP-HBs\/c resulted in modest immune activation and limited antiviral effects in HBV-carrier mice. In contrast, substituting the modified vaccinia virus Ankara (MVA)-HBs\/c boost in the TherVacB regimen with VSV-GP-HBs\/c elicited robust HBV-specific antibody responses and strong CD4 and CD8 T-cell immunity, assessed by intracellular IFN-\u03b3 staining after peptide stimulation. This regimen achieved a substantial reduction in serum HBsAg levels, numbers of HBV-positive hepatocytes, and intrahepatic HBV-DNA, with antiviral efficacy comparable to that of the classical TherVacB regimen. Notably, a second viral vector boost did not enhance HBV-specific immunity or antiviral efficacy; instead, it promoted dominant vector-specific CD8 T-cell responses. Long-term analyses performed 10 weeks after the last vaccination further demonstrated that a single protein-prime\/VSV-GP-HBs\/c boost was sufficient to achieve sustained antiviral control. Conclusions: These findings identify VSV-GP-HBs\/c as an effective boost vector for therapeutic hepatitis B vaccination and establish protein priming followed by a single viral vector boost as an optimal strategy for sustained antiviral immunity.<\/jats:p>","DOI":"10.3390\/vaccines14030266","type":"journal-article","created":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T10:10:43Z","timestamp":1773655843000},"page":"266","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Protein Priming Followed by a Replication-Competent VSV-GP Vector Boost Induces Sustained Immune Control in Therapeutic Hepatitis B Vaccination"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8853-3834","authenticated-orcid":false,"given":"Jinpeng","family":"Su","sequence":"first","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Munich, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Partner Site, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna D.","family":"Kosinska","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Munich, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Partner Site, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanne","family":"Miko","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Munich, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4604-4765","authenticated-orcid":false,"given":"Edanur","family":"Ates \u00d6z","sequence":"additional","affiliation":[{"name":"Institute of Virology, Technical University of Munich\/Helmholtz Munich, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Partner Site, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dorothee von","family":"Laer","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-7905","authenticated-orcid":false,"given":"Janine","family":"Kimpel","sequence":"additional","affiliation":[{"name":"Institute of Virology, Medical University of Innsbruck, 6020 Innsbruck, Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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 Munich, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Munich Partner Site, 81675 Munich, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,16]]},"reference":[{"key":"ref_1","unstructured":"(2025, November 20). 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