Here we report that therapeutic heterologous protein-prime/MVA-vector-boost vaccination against hepatitis B synergizes with CpG-application to enhance numbers and functionality of HBcAg-specific CD8 T-cells in presence of high HBV-antigen levels in two preclinical models of persistent HBV infection, i.e. the AAV-HBV model and HBV-transgenic mice. The gene discussed is CD8A; the disease is hepatitis B virus infection.