Hepatitis B virus surface antigen and core antigen (HBsAg and HBcAg)

Hepatitis B virus surface antigen (HBsAg) and core antigen (HBcAg) are the primary structural proteins of the Hepatitis B virus (HBV) and represent critical targets for both preventative and therapeutic interventions. HBsAg is the major envelope glycoprotein, existing in small, medium, and large isoforms, and is essential for viral attachment and entry into hepatocytes via the NTCP receptor [1.1.1, 1.1.5]. It is produced in vast excess as non-infectious subviral particles that act as an immunological decoy, exhausting the host's innate and adaptive immune responses [1.1.5, 1.4.4]. HBcAg is the structural subunit of the icosahedral nucleocapsid that encloses the viral DNA and polymerase, playing a vital role in viral assembly, genome packaging, and the transport of the viral genome to the host nucleus [1.3.1, 1.3.2]. In chronic HBV infection, the persistence of these antigens is linked to immune tolerance, liver cirrhosis, and the development of hepatocellular carcinoma [1.1.2, 1.4.4]. Current therapeutic strategies include HBsAg-neutralizing antibodies to restore immune activity, capsid assembly modulators (CAMs) that target HBcAg to disrupt the viral life cycle, and RNA-targeted therapies that silence the production of both proteins to achieve a functional cure [1.2.2, 1.4.2].

Other names

HBV surface antigenHBV core antigenAustralia antigenHepatitis B capsid proteinC proteinHBcHepatitis B virus antigens

Drugs targeting these antigens operate through distinct pathways: HBsAg-targeting agents, such as preventative vaccines and therapeutic monoclonal antibodies, neutralize circulating virions and subviral particles to prevent hepatocyte entry and alleviate HBsAg-induced immune suppression. HBcAg-targeting agents, known as capsid assembly modulators (CAMs), interfere with the precise assembly of the viral nucleocapsid, thereby preventing the packaging of pregenomic RNA and the formation of infectious virions. Additionally, RNA interference (RNAi) and antisense oligonucleotide (ASO) therapies target the viral mRNA transcripts to silence the production of both HBsAg and HBcAg simultaneously.