Qui trovate le pubblicazioni scientifiche e gli articoli tecnici dei partner del progetto TherVacB. Scorri in basso per saperne di più sull’epatite cronica B, sul virus, sullo screening e sui test per l’epatite C e B, sulla vaccinazione terapeutica e sulla ricerca di cure.
Closing in on a cure for hepatitis B
30 March 2022 | Nature
Finite courses of treatment could get the virus under control — with the right combination of drugs.
Read on to know more how TherVacB’s Ulrike Protzer and Mala Maini together with other leading HBV scientists, virologists, viral immunologists and hepatologists around the world have pushed the development of an HBV cure-focused action plan that includes patient perspectives.
Immunogenicity and Antiviral Response of Therapeutic Hepatitis B Vaccination in a Mouse Model of HBeAg-Negative, Persistent HBV Infection
31 July 2021 | Vaccines
Anna D Kosinska, Julia Festag, Martin Mück-Häusl, Marvin M Festag, Theresa Asen, Ulrike Protzer
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.
Screening auf Hepatitis B und C gehört jetzt zur Gesundheitsvorsorge
17 June 2021 | Der Hausarzt.DIGITAL
Kürzlich wurden Tests auf Hepatitis B und C in die Gesundheitsvorsorge (“Check-up”) aufgenommen. Versicherte ab 35 Jahren können sich einmalig auf diese beiden Erkrankungen untersuchen lassen. Dr. med. Ulrich Scharmer sprach darüber mit der Virologin Prof. Dr. med. Ulrike Protzer, München.
PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B
18 March 2021 | Biomolecules
Till Bunse, Anna D. Kosinska, Thomas Michler and Ulrike Protzer
In chronic hepatitis B virus (HBV) infection, virus-specific T cells are scarce and partially dysfunctional. Therapeutic vaccination is a promising strategy to induce and activate new virus-specific T cells. In long-term or high-level HBV carriers, however, therapeutic vaccination by itself may not suffice to cure HBV. One reason is the impairment of antiviral T cells by immune checkpoints. In this study, we used small-interfering RNA (siRNA) in combination with a heterologous prime-boost therapeutic vaccination scheme (TherVacB) to interfere with a major immune checkpoint, the interaction of programmed death protein-1 (PD-1) and its ligand (PDL-1). In mice persistently replicating HBV after infection with an adeno-associated virus harboring the HBV genome, siRNA targeting PD-L1 resulted in a higher functionality of HBV-specific CD8+ T cells after therapeutic vaccination, and allowed for a more sustained antiviral effect and control of HBV in peripheral blood and in the liver. The antiviral effect was more pronounced if PD-L1 was down-regulated during prime than during boost vaccination. Thus, targeting PD-L1 using siRNA is a promising approach to enhance the efficacy of therapeutic vaccination and finally cure HBV.