A bi-functional hepatitis B virus core antigen (HBcAg) chimera activates HBcAg-specific T cells and preS1-specific antibodies

A major problem in chronic hepatitis B virus (HBV) infection is that treatment with specific antivirals is life-long since they rarely induce a sustained response. An attractive option is therefore to combine antiviral therapy with some type of immune stimulator, such as a therapeutic vaccine. Several lines of evidence suggest that a key target for the cellular immune response is the HBV core antigen (HBcAg). However, it may also be of advantage to simultaneously improve the neutralizing antibody response to the surface (S) region of HBV. We therefore generated chimeric HBcAg particles expressing preS1 residues 1-42 at the tip of the spike region. We could show that this chimeric HBcAg-preS1 protein primed both HBcAg-specific T cells and antibodies to preS1. This strongly suggests that this may be a viable approach to develop an effective bi-functional therapeutic vaccine as an add-on for the treatment of chronic HBV infections.