Restoring T cell function to promote resolution of chronic HBV infection

Abstract An estimated 296 million people worldwide suffer from chronic hepatitis B virus (HBV) infection, with 1.5 new infections occurring each year despite the availability of an effective vaccine. Chronic HBV infection persists in a dysfunctional immune environment, manifested by ineffective T cell response to virus. Patient HBV-specific CD8 +T cells have diminished proliferative capacity and cytokine production, they exhibit increased sustained expression inhibitory checkpoint receptors. In mice persistent replication, reduction viral antigens can be achieved therapeutic immunization alphavirus- vesiculovirus-based vaccine platforms expressing antigens. However, blocking PD-1 CTLA-4 signaling may further enhance antiviral effector function efficacy. Using mouse model replication which are transduced adeno-associated encoding genome (AAV-HBV), we investigated role these receptors HBV. Antibody-mediated blockade either or independently AAV-HBV did not promote clearance. Likewise, inhibition combined VSV antigen improve anti-HBV responses clearance high-antigen replication. lower initial loads, along resulted enhanced decrease circulating antigen. These results suggest methodologies for improving functional cure infection. Supported National Institute Allergy Infectious Diseases Diabetes Digestive Kidney Institutes Health under award numbers R01AI148354 R44DK113858. The content is solely responsibility authors does necessarily represent official views Health.