Hepatitis B virus antigens and Hepatitis B virus polymerase (HBV antigens / HBV Pol)

Hepatitis B virus (HBV) antigens and the HBV polymerase/reverse transcriptase are the primary targets in the combined therapeutic strategy involving GS-4774 and oral nucleos(t)ide analogues (NAs). The HBV polymerase is a multifunctional enzyme (UniProt P03146) responsible for the replication of the viral genome through reverse transcription of pregenomic RNA, making it the standard target for suppressive antiviral therapy like tenofovir or entecavir (LiverTox, NIH). HBV antigens, including the surface (HBsAg), core (HBcAg), and X (HBx) proteins, serve as targets for the immune system; GS-4774 is a yeast-based immunotherapy (Tarmogen) designed to deliver these antigens to dendritic cells to provoke a robust T-cell response (PMID: 27102901). This combination therapy is intended to overcome the immune exhaustion characteristic of chronic HBV infection while maintaining viral suppression (PMID: 29113913). By targeting both the replication machinery and the host's immune tolerance, the goal is to achieve HBsAg loss, which is considered a functional cure for the disease.

Other names

Hepatitis B surface antigen (HBsAg)Hepatitis B core antigen (HBcAg)Hepatitis B X protein (HBx)Hepatitis B virus DNA polymeraseHepatitis B virus reverse transcriptaseHBV P protein

GS-4774 induces T-cell mediated immune responses against HBV-infected cells by delivering HBV antigens via a yeast vector (PMID: 27102901); oral antivirals inhibit HBV DNA synthesis by acting as nucleos(t)ide analogue inhibitors of the HBV polymerase/reverse transcriptase (LiverTox, NIH).