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Su, J. ; Kosinska, A. ; Miko, S. ; Ates Öz, E. ; Laer, D.v.* ; Kimpel, J.* ; Protzer, U.

Protein priming followed by a replication-competent VSV-GP vector boost induces sustained immune control in therapeutic hepatitis B vaccination.

Vaccines 14:266 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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-naïve 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-γ 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Vaccination ; Viral Vector ; Immune System ; Antigen ; Hbsag ; Hepatitis B Virus ; Adjuvant ; Antibody ; Vaccinia; Vesicular Stomatitis-virus; T-cells; Adaptive Immunity; Pathogenesis; Adenovirus; Vaccines
e-ISSN 2076-393X
Journal Vaccines
Quellenangaben Volume: 14, Issue: 3, Pages: , Article Number: 266 Supplement: ,
Publisher MDPI
Publishing Place Basel
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
Grants German Center for Infection Research
Bundesministerium für Forschung, Technologie und Raumfahrt
EU Horizon 2020
German Research Foundation