Novel Hepatitis B Vaccine and Immunotherapy

Project Summary Hepatitis B virus (HBV) infects over 250 million people worldwide and is a leading cause of liver cirrhosis and cancer in many countries. The unique life cycle of HBV involves the generation of covalently closed circular double stranded DNA (cccDNA) in the nucleus of an infected cell for

viral gene transcription and persistence. Current treatments only suppress viral replication. To cure HBV, it will likely require a combination of drugs targeting the virus as well as boosting antiviral immunity. In this project, we will apply the mRNA vaccine technology as a potent vaccine and immunotherapy against HBV. A major scientific challenge is that the HBV vaccine

antigen, S, can disrupt protein homeostasis (proteostasis) leading to protein accumulation and undesirable ER stress in the mammalian cells overexpressing the protein. We will investigate the viral and cellular factors that hinder effective antigen expression, and improve the vaccine antigens for elicitation of potent antibody and T cell responses to cure HBV infection. Success in

this project will also create new opportunities in the development of a multivalent mRNA vaccine against common human pathogens.