PuSH - Publikationsserver des Helmholtz Zentrums München

Kosinska, A. ; Kächele, M. ; Kerth, H.A. ; Mück-Häusl, M. ; Ates Öz, E. ; Gültan, M. ; Hansen-Palmus, L. ; Sacherl, J. ; Ko, C. ; Festag, J. ; Lehmann, M.H.* ; Mogler, C.* ; Steiger, K.* ; Knolle, P.A.* ; Bauer, T. ; Volz, A.K.* ; Protzer, U.

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

Mol. Ther. Nucleic Acids 36:102641 (2025)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
Altmetric
Weitere Metriken?
[➜Einloggen]
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Hbv ; Mt: Delivery Strategies ; Mva ; Thervacb ; Chronic Hepatitis B ; Heterologous Prime Boost ; Therapeutic Vaccination ; Viral Vector; Boost Vaccination; Surface-antigen; Viral Clearance; X Protein; Cells; Immunogenicity; Regimen
ISSN (print) / ISBN 2162-2531
e-ISSN 2162-2531
Zeitschrift Molecular therapy - Nucleic Acids
Quellenangaben Band: 36, Heft: 3, Seiten: , Artikelnummer: 102641 Supplement: ,
Verlag Elsevier
Verlagsort New York, NY
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen German Center for Infection Research (DZIF)
C-NATM - Cluster for Nucleic Acid Therapeutics Munich - Clusters4Future initiative
German Ministry for Education and Research (BMBF) via the TherVacB PLUS project
German Center for Infection Research via project TTU 05.803 HBV Cure
EU Horizon 2020 consortium TherVacB
PoC initiative by the Helmholtz and Fraunhofer Associations
German Research Foundation via TRR179