MVA-HBVac—A novel vaccine vector that allows pan-genotypic targeting of hepatitis B virus by therapeutic vaccination

• Published in: Molecular therapy. Nucleic acids Vol. 36; no. 3; p. 102641
• Main Authors: Kosinska, Anna D., Kächele, Martin, Kerth, Helene A., Mück-Häusl, Martin, Ates Öz, Edanur, Gültan, Merve, Hansen-Palmus, Lea, Sacherl, Julia, Ko, Chunkyu, Festag, Julia, Lehmann, Michael H., Mogler, Carolin, Steiger, Katja, Knolle, Percy A., Bauer, Tanja, Volz, Asisa K., Protzer, Ulrike
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.09.2025; American Society of Gene & Cell Therapy; Elsevier
• Subjects: chronic hepatitis B; HBV; heterologous prime boost; MT: Delivery Strategies; MVA; Original; therapeutic vaccination; TherVacB; viral vector; chronic hepatitis B; therapeutic vaccination; TherVacB; MVA; viral vector; MT: Delivery Strategies; HBV; heterologous prime boost
• ISSN: 2162-2531; 2162-2531
• DOI: 10.1016/j.omtn.2025.102641

Therapeutic vaccination holds the promise to cure chronic hepatitis B virus (HBV) infection. We hypothesize that B cell, CD4, and CD8 T cell responses are necessary to overcome HBV-specific immune tolerance in chronic infection because they accompany the rare, spontaneous resolution of chronic HBV infection. Therefore, we designed the heterologous prime-boost vaccine TherVacB in which virus-like particle vaccination stimulates B and helper CD4 T cells and primes cytotoxic effector CD8 T cells and a vector boost expands the T cell response. Here, we report the generation and characterization of a novel modified vaccinia virus Ankara (MVA)-based vector, MVA-HBVac, capable of inducing strong and multi-specific T cell responses against the immunodominant epitopes of four different viral proteins covering >95% of HBV strains circulating worldwide. When MVA-HBVac was administered after a prime with adjuvanted hepatitis B S- and core-antigens forming virus-like particles, it activated strong HBV-specific CD4 and CD8 T cell responses against the major HBV antigens in vivo in naive and HBV carrier mice. This induced a sustained antiviral effect against different, clinically relevant HBV genotypes. Our data showed that the TherVacB regimen employing the novel, pan-genotypic MVA-HBVac vector could overcome HBV-specific immune tolerance and lead to the initiation of clinical trials evaluating the therapeutic vaccine. [Display omitted] Ulrike Protzer and colleagues developed a novel therapeutic hepatitis B vaccine vector, MVA-HBVac, designed to target 95% of circulating HBV isolates worldwide. Administration of MVA-HBVac following two protein prime immunizations in the TherVacB vaccination scheme induced strong HBV-specific T cell responses and reduced or even “cured” HBV in mice carrying various HBV genotypes.