ArticleJHEP reports : innovation in hepatology2026
Therapeutic vaccination strategy targeting the PreS1 region of L-HBsAg for HBV/HDV co-infection.
Article in JHEP reports : innovation in hepatology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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12 authors.
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Abstract
BACKGROUND &
aimsAchieving functional cure for chronic hepatitis B (CHB) will likely require a combinatorial approach targeting multiple aspects of the complex HBV life cycle and host adaptive immune responses. Here, we developed a therapeutic vaccination strategy targeting the PreS1 region of L-HBsAg, required for cellular entry of both HBV and HDV.
methodsAn established, potent T-cell-inducing platform, recombinant adenovirus (Ad), was used as a nanoparticle scaffold for PreS1 attachment to generate antibodies that neutralise virus entry and establish T-cell-mediated immune control. Ad particles encoding multiple HBV antigens were decorated with the PreS1 peptide using the DogTag/DogCatcher protein superglue. The immunogenicity of PreS1-decorated Ad was assessed in C57B/6 mice using IgG ELISA, serum neutralisation assays, INF-γ ELISpot, and intracellular cytokine staining.
resultsScreening a cohort of 61 patients diagnosed with CHB revealed minimal evidence of natural anti-PreS1 responses. Mice vaccinated with PreS1-decorated Ad induced robust anti-PreS1 antibody responses that neutralised HBV (p <0.01) and HDV (p <0.05) infections. By contrast, an undecorated Ad encoding L-HBsAg failed to neutralise HBV, demonstrating that PreS1 decoration was required for potent neutralisation of HBV. Strong CD8
conclusionsPreS1-decorated Ad combines immunological inhibition of HBV and HDV entry with potent anti-HBV T-cell induction in a single platform, providing a promising addition to current therapeutic strategies against CHB, with particular utility in HBV/HDV co-infection. IMPACT AND IMPLICATIONS: A functional cure for chronic hepatitis B is urgently needed, and given the complexity of the disease, achieving this will likely require combination therapies that target multiple stages of the viral lifecycle. Here, we developed a therapeutic vaccination strategy that combines PreS1-targeted entry inhibition with induction of T-cell responses against multiple HBV antigens by decorating adenovirus particles encoding L-HBsAg and HBcAg with PreS1 peptide. In mice, PreS1-decorated adenovirus particles induced serum neutralising activity against both HBV and HDV and robust T-cell responses against encoded HBV antigens. Our findings suggest that PreS1-decorated adenoviral vaccines could complement existing therapeutic approaches for viral hepatitis.
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