Hepatitis B virus pre-S2 protein (pre-S2)

The Hepatitis B virus pre-S2 protein is a structural component of the middle (M) and large (L) surface antigens of the Hepatitis B virus (HBV). It is encoded by the S gene and is produced when translation begins at the second start codon, resulting in a protein that includes the pre-S2 domain and the small (S) antigen (UniProt P03142). The pre-S2 domain plays a vital role in the viral life cycle by mediating the attachment of the virus to host hepatocytes and facilitating the assembly and secretion of subviral particles and mature virions (PMID: 11559017). It contains a binding site for polymerized human serum albumin, which is thought to act as a bridge between the virus and the host cell receptor. In clinical applications, the pre-S2 protein is a key component of third-generation HBV vaccines, such as PreHevbrio, which are designed to be more immunogenic than traditional S-only vaccines by providing additional T-cell and B-cell epitopes (PMID: 34847130). Furthermore, antibodies targeting the pre-S2 region are highly neutralizing and are being explored for therapeutic use to prevent reinfection in liver transplant patients and to treat chronic HBV infections.

Other names

Middle surface proteinM-HBsAgHBV Middle S proteinpre-S2 domainHepatitis B virus envelope protein M

Induction of neutralizing antibodies that block viral attachment and entry into hepatocytes; competitive inhibition of viral binding sites.