title: A human monoclonal antibody against small envelope protein of hepatitis B virus with potent neutralization effect.
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.
authors.affiliation: a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.affiliation: b Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention , China.
authors.forename: Lina
authors.initials: L
authors.lastname: Sun
authors.affiliation: a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
authors.forename: Tiansheng
authors.initials: T
authors.lastname: Li
authors.affiliation: c Putuo District Center Hospital, Shanghai University of Traditional Chinese Medicine , Shanghai , China.
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Ma
authors.affiliation: d Liver Research Center, The Warren Alpert School of Medicine, Brown University , Providence , Rhode Island , USA.
authors.forename: Jisu
authors.initials: J
authors.lastname: Li
authors.affiliation: b Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: b Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention , China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Li
authors.affiliation: a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
authors.forename: Youhua
authors.initials: Y
authors.lastname: Xie
authors.affiliation: a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
authors.forename: Yumei
authors.initials: Y
authors.lastname: Wen
authors.affiliation: b Key Laboratory for Medical Virology, NHFPC, National Institute for Viral Disease Control and Prevention , China.
authors.forename: Mifang
authors.initials: M
authors.lastname: Liang
authors.affiliation: a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: a Department of Pathobiology and Key Laboratory of Medical Molecular Virology , School of Basic Medical Sciences, Fudan University , Shanghai , China.
authors.forename: Shuping
authors.initials: S
authors.lastname: Tong
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D057134:Antibodies, Neutralizing / Q000276:immunology / Q000494:pharmacology; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004195:Disease Models, Animal; D005260:Female; D006509:Hepatitis B / Q000188:drug therapy / Q000276:immunology; D006510:Hepatitis B Antibodies / Q000276:immunology / Q000494:pharmacology; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D006801:Humans; D008297:Male; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens
keywords: Anti-S; hepatitis B immune globulin; hepatitis B virus; human monoclonal antibody; neutralization; small envelope protein; transgenic mice