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Immunogenicity and antiviral response of therapeutic hepatitis B vaccination in a mouse model of hbeag-negative, persistent hbv infection.

Vaccines 9:841 (2021)
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During the natural course of chronic hepatitis B virus (HBV) infection, the hepatitis B e antigen (HBeAg) is typically lost, while the direct transmission of HBeAg-negative HBV may result in fulminant hepatitis B. While the induction of HBV-specific immune responses by therapeutic vaccination is a promising, novel treatment option for chronic hepatitis B, it remains unclear whether a loss of HBeAg may influence its efficacy or tolerability. We therefore generated an adeno-associated virus (AAV)-vector that carries a 1.3-fold overlength HBV genome with a typical stop-codon mutation in the pre-core region and initiates the replication of HBeAg(−) HBV in mouse livers. Infection of C57BL/6 mice established persistent HBeAg(−) HBV-replication without any detectable anti-HBV immunity or liver damage. HBV-carrier mice were immunized with TherVacB, a therapeutic hepatitis B vaccine that uses a particulate HBV S and a core protein for prime vaccination, and a modified vaccinia Ankara (MVA) for boost vaccination. The TherVacB immunization of HBeAg(+) and HBeAg(−) HBV carrier mice resulted in the effective induction of HBV-specific antibodies and the loss of HBsAg but only mild liver damage. Intrahepatic, HBV-specific CD8 T cells induced in HBeAg(−) mice expressed more IFNγ but showed similar cytolytic activity. This indicates that the loss of HBeAg improves the performance of therapeutic vaccination by enhancing non-cytolytic effector functions.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Chronic Hepatitis B ; Hepatitis B Virus ; Hepatitis B Virus E Antigen ; Pre-core Mutation ; Prime/boost Vaccination ; Therapeutic Vaccination; T-cells; Virus-dna; E-antigen; Precore Region; Mutations; Seroconversion; Expression; Clearance; Fulminant; Protein
e-ISSN 2076-393X
Zeitschrift Vaccines
Quellenangaben Band: 9, Heft: 8, Seiten: , Artikelnummer: 841 Supplement: ,
Verlag MDPI
Verlagsort Basel
Begutachtungsstatus Peer reviewed
Förderungen Helmholtz Association
Horizon 2020 Framework Programme
Deutsche Forschungsgemeinschaft