Inhibition of preS1-hepatocyte interaction by an array of recombinant human antibodies from naturally recovered individuals

Sci Rep. 2016 Feb 18:6:21240. doi: 10.1038/srep21240.

Abstract

Neutralizing monoclonal antibodies are being found to be increasingly useful in viral infections. In hepatitis B infection, antibodies are proven to be useful for passive prophylaxis. The preS1 region (21-47a.a.) of HBV contains the viral hepatocyte-binding domain crucial for its attachment and infection of hepatocytes. Antibodies against this region are neutralizing and are best suited for immune-based neutralization of HBV, especially in view of their not recognizing decoy particles. Anti-preS1 (21-47a.a.) antibodies are present in serum of spontaneously recovered individuals. We generated a phage-displayed scFv library using circulating lymphocytes from these individuals and selected four preS1-peptide specific scFvs with markedly distinct sequences from this library. All the antibodies recognized the blood-derived and recombinant preS1 containing antigens. Each scFv showed a discrete binding signature, interacting with different amino acids within the preS1-peptide region. Ability to prevent binding of the preS1 protein (N-terminus 60a.a.) to HepG2 cells stably expressing hNTCP (HepG2-hNTCP-C4 cells), the HBV receptor on human hepatocytes was taken as a surrogate marker for neutralizing capacity. These antibodies inhibited preS1-hepatocyte interaction individually and even better in combination. Such a combination of potentially neutralizing recombinant antibodies with defined specificities could be used for preventing/managing HBV infections, including those by possible escape mutants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Neutralizing / immunology*
  • Antibodies, Neutralizing / pharmacology
  • Antibodies, Viral / immunology*
  • Antibodies, Viral / pharmacology
  • Hep G2 Cells
  • Hepatitis B Surface Antigens* / immunology
  • Hepatitis B virus / immunology*
  • Hepatocytes / immunology*
  • Hepatocytes / virology
  • Humans
  • Protein Precursors* / antagonists & inhibitors
  • Protein Precursors* / immunology
  • Recombinant Proteins / immunology
  • Recombinant Proteins / pharmacology
  • Single-Chain Antibodies / immunology*
  • Single-Chain Antibodies / pharmacology

Substances

  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Hepatitis B Surface Antigens
  • Protein Precursors
  • Recombinant Proteins
  • Single-Chain Antibodies
  • presurface protein 1, hepatitis B surface antigen