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

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

Author information

1
a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
2
b Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention , China.
3
c Putuo District Center Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai , China.
4
d Liver Research Center, The Warren Alpert School of Medicine, Brown University , Providence , Rhode Island , USA.

Abstract

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

PMID:
26713590
PMCID:
PMC4966830
DOI:
10.1080/19420862.2015.1134409
[Indexed for MEDLINE]
Free PMC Article

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