Hepatitis Delta Virus Infection Increases the Efficacy of HBV-Specific T Cell-Based Therapies

Hepatitis Delta virus (HDV) requires hepatitis B virus (HBV) to complete its infection cycle and causes a severe hepatitis with limited therapeutic options. To determine the prospect of T cell therapy in HBV/HDV co-infection, we first studied the HDV impact on viral antigen processing and presentation. Utilizing in vitro models of HBV/HDV co-infection, we demonstrated that HDV boosts HBV epitope presentation, both in HBV/HDV co-infected and neighboring mono-HBV infected cells through up-regulation of antigen processing pathway mediated by IFN-beta/lambda. This up-regulation was confirmed in liver biopsies of HBV/HDV patients. We then demonstrated in vitro and in HBV/HDV preclinical mouse model that HDV increases antiviral efficacy of HBV-specific T cell receptors engineered T cells. Thus, by unveiling the effect of HDV on HBV antigen presentation, we provide a framework to better understand HBV/HDV immune pathology, and we advocate the use of engineered HBV-specific T cells for the treatment of HBV/HDV co-infection.