A human monoclonal antibody against small envelope protein of hepatitis B virus with potent neutralization effect

MAbs. 2016;8(3):468-77. doi: 10.1080/19420862.2015.1134409. Epub 2015 Dec 29.


Hepatitis B virus (HBV) produces large (L), middle (M), and small (S) envelope proteins, alternatively referred to as hepatitis B surface antigen (HBsAg). Currently, yeast-derived S protein serves as the preventive vaccine, while hepatitis B immune globulin (HBIG) concentrated from pooled plasma of vaccine recipients is employed for post-exposure prophylaxis. However, only a small proportion of the antibodies in HBIG are HBV specific. In the present study, a human monoclonal anti-S antibody (G12) was developed, produced under GLP conditions, and subjected to a panel of functional assays. In vitro results demonstrated high affinity of G12 for the S protein (KD = 7.56 nM). It reacted with envelope proteins of all 7 HBV genotypes tested (A-F, H) by immunofluorescent staining, and more than 97% of HBsAg-positive patient serum samples by enzyme-linked immunosorbent assay. G12 recognized a conformational epitope, although the exact sequence remains unknown. Strikingly, G12 was at least 1,000-fold more potent than HBIG in neutralizing HBV infectivity in both HepaRG cell line and HepG2 cells reconstituted with the HBV receptor. In a transgenic mouse model of HBV persistence, a single peritoneal injection of G12 markedly diminished serum HBsAg titers in all 7 mice, which was sustained for the observation period of 144 d in mice with low pre-treatment levels. While the therapeutic potential of G12 warrants further investigation using a large number of animals, G12 is a potent neutralizing human monoclonal antibody and a promising candidate to replace or supplement HBIG in the prevention of HBV infection.

Keywords: Anti-S; hepatitis B immune globulin; hepatitis B virus; human monoclonal antibody; neutralization; small envelope protein; transgenic mice.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / immunology
  • Antibodies, Monoclonal* / pharmacology
  • Antibodies, Neutralizing* / immunology
  • Antibodies, Neutralizing* / pharmacology
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Disease Models, Animal
  • Female
  • Hepatitis B Antibodies* / immunology
  • Hepatitis B Antibodies* / pharmacology
  • Hepatitis B Surface Antigens / immunology*
  • Hepatitis B virus / immunology*
  • Hepatitis B* / drug therapy
  • Hepatitis B* / immunology
  • Humans
  • Male
  • Mice


  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Hepatitis B Antibodies
  • Hepatitis B Surface Antigens