Sci Rep. 2019 Jul 25;9(1):10808. doi: 10.1038/s41598-019-47149-w.
Synergy of therapeutic heterologous prime-boost hepatitis B vaccination with CpG-application to improve immune control of persistent HBV infection.
Kosinska AD1,2,3, Moeed A4, Kallin N4, Festag J1,2, Su J1,2, Steiger K5, Michel ML6, Protzer U7,8,9, Knolle PA10,11.
Author information
1
Institute of Virology, Technical University of Munich, Munich, Germany.
2
Helmholtz Centre Munich, Munich, Germany.
3
German Center for Infection Research (DZIF), Partner site München, Munich, Germany.
4
Institute of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany.
5
Institute of Pathology, Technical University of Munich, Munich, Germany.
6
Institute Pasteur, Paris, France.
7
Institute of Virology, Technical University of Munich, Munich, Germany. [email protected].
8
Helmholtz Centre Munich, Munich, Germany. [email protected].
9
German Center for Infection Research (DZIF), Partner site München, Munich, Germany. [email protected].
10
Institute of Molecular Immunology and Experimental Oncology, Technical University of Munich, Munich, Germany. [email protected].
11
German Center for Infection Research (DZIF), Partner site München, Munich, Germany. [email protected].
Abstract
Therapeutic vaccination against chronic hepatitis B must overcome high viral antigen load and local regulatory mechanisms that promote immune-tolerance in the liver and curtail hepatitis B virus (HBV)-specific CD8 T cell immunity. Here, we report that therapeutic heterologous HBcore-protein-prime/Modified-Vaccinia-Virus-Ankara (MVA-HBcore) boost vaccination followed by CpG-application augmented vaccine-induced HBcAg-specific CD8 T cell-function in the liver. In HBV-transgenic as well as AAV-HBV-transduced mice with persistent high-level HBV-replication, the combination of therapeutic vaccination with subsequent CpG-application was synergistic to generate more potent HBV-specific CD8 T cell immunity that improved control of hepatocytes replicating HBV.