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The Hepatitis B virus middle surface protein (MHBs), which contains the pre-S2 surface antigen, is a key component of the HBV envelope. It is produced by the translation of the pre-S2/S mRNA and consists of the S protein sequence with an additional 55 amino acids at the N-terminus (UniProt P03142). This protein is essential for the viral life cycle, facilitating the attachment of the virus to the host cell membrane and contributing to the secretion of subviral particles (Glebe & Bremer, 2013). In clinical practice, the pre-S2 region is highly immunogenic; antibodies targeting this domain are often the first to appear during acute infection and are linked to protective immunity (Neurath et al., 1984). Consequently, it is a primary component in third-generation vaccines like PreHevbrio, which aim to provide broader protection and overcome non-responsiveness seen with traditional S-antigen vaccines (Vesikari et al., 2021). Furthermore, mutations or deletions in the pre-S2 region are clinically significant as they are frequently associated with chronic infection progression and an increased risk of hepatocellular carcinoma due to endoplasmic reticulum stress (Pollicino et al., 2014).
Induction of neutralizing antibodies (anti-pre-S2) that block viral attachment to hepatocytes and enhance the overall immune response against the virus (Vesikari et al., 2021; Neurath et al., 1984).
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