HBV Pres1 Specific Neutra™ Antibody Products

Hepatitis B virus (HBV) is a DNA virus which infects the liver, leading to conditions such as acute hepatitis, cirrhosis, chronic liver disease, and hepatocellular carcinoma (HCC). It is transmitted through blood, sexual contact, or from mother to child. HBV is highly prevalent worldwide, with higher rates in Asia and sub-Saharan Africa. Vaccination and antiviral drugs effectively prevent HBV infection. New therapeutics such as antibodies may improve antiviral efficacy while mitigating or delaying the emergence of drug resistance. The HBV preS1 region is a key part of the virus's surface protein, playing a critical role in the virus's ability to enter liver cells and establish infection.

preS1 Surface Protein of HBV

HBV has a partially double-stranded DNA genome encased in a core protein shell, surrounded by an envelope containing surface proteins. The envelope includes three major surface proteins: large (LHB), middle (MHB), and small (SHB), with the large protein containing the preS1 and preS2 domains. The preS1 region is located at the N-terminal of the LHB protein and plays a critical role in viral entry. The preS1 protein contains the viral putative hepatocyte binding domain between 21–47 amino acids, which can bind to specific receptors on hepatocyte surfaces. The preS1 domain’s structure includes amphipathic α-helices, crucial for receptor interaction.

Fig. 1 The structure of HBsAg isoforms.^{1, 4}

preS1 in HBV Infection

The preS1 region of the HBV surface protein is essential for the HBV life cycle, particularly in viral entry into hepatocytes. It binds to the sodium taurocholate cotransporting polypeptide (NTCP) receptor on liver cells, initiating virus attachment and internalization. Once inside the cell, preS1 aids in HBV replication by interacting with cellular machinery, influencing viral DNA synthesis and assembly. PreS1 can also serve as a biomarker for HBV infection, as its presence correlates with active viral replication and severity of liver disease. Elevated levels of preS1 are linked to chronic HBV infections and may indicate progression to cirrhosis or HCC. Mutations or lesions in the preS1 domain can affect viral infectivity, leading to changes in disease severity or resistance to immune responses.

Fig. 2 The relationship between deletions in the HBV pre-S gene and the progression of liver disease, as well as the development and recurrence of HCC.^{2, 4}

HBV preS1 Neutralizing Antibodies

PreS1 is a crucial region for HBV infection and a potential therapeutic target. Neutralizing monoclonal antibodies (mAbs) have proven useful in viral infections, including hepatitis B, where they are effective for passive prophylaxis. Antibodies targeting the preS1 region are especially effective in neutralizing HBV, as they do not recognize decoy particles. These anti-preS1 antibodies block the viral attachment, endocytosis, and potentially membrane penetration into hepatocytes by targeting the viral hepatocyte-binding domain. Several murine and humanized preS1-specific mAbs have been developed, showing success in neutralizing HBV in non-human primates. One study isolated recombinant human monoclonal scFvs from recovered hepatitis B patients, effectively blocking preS1-peptide binding to hNTCP in HepG2-hNTCP C4 cells.

Fig. 3 Effect of HBV infection and human mAbs targeting HBV envelope protein.^{3, 4}

Creative Biolabs offers a series of anti-HBV preS1 neutralizing antibodies with high specificity and efficacy, which can be an ideal option for your research on hepatitis B prophylaxis and therapeutic development.

REFERENCES

1. Lazarevic, Ivana, et al. "Hepatitis B surface antigen isoforms: Their clinical implications, utilisation in diagnosis, prevention and new antiviral strategies." Pathogens 13.1 (2024): 46.
2. Lin, Yueh-Te, et al. "Hepatitis B virus Pre-S gene deletions and Pre-S deleted proteins: clinical and molecular implications in hepatocellular carcinoma." Viruses 13.5 (2021): 862.
3. Cerino, Antonella, et al. "Human monoclonal antibodies as adjuvant treatment of chronic hepatitis B virus infection." Frontiers in immunology 10 (2019): 2290.
4. Distributed under Open Access license CC BY 4.0, without modification.