title: Analysis of the epitope and neutralizing capacity of human monoclonal antibodies induced by hepatitis B vaccine.
abstract: Hepatitis B virus (HBV) is an infectious agent that is a significant worldwide public health issue. However, the mechanism by which vaccination-induced antibodies prevent HBV infection remains unclear. To investigate the mechanism by which antibodies induced by hepatitis B surface Ag (HBsAg)-vaccination prevent HBV infection in humans, we prepared human monoclonal antibodies (mAbs) against HBsAg using a novel cell-microarray system from peripheral blood B-lymphocytes from vaccinated individuals. We then characterized the IgG subclass, L-chain subtype, and V-gene repertoire of the H/L-chain, as well as affinities of each of these mAbs. We also determined the epitopes of the individual mAbs using synthesized peptides, and the HBV-neutralizing activities of mAbs using the hepatocyte cell line HepaRG. Consequently, IgG1 and kappa chain was mainly used as the mAbs for HBsAg. Seventy percent of the mAbs bound to the loop domain of the small-HBsAg and showed greater neutralizing activities. There were no relationships between their affinities and neutralization activities. A combination of mAbs recognizing the first loop domain showed a synergistic effect on HBV-neutralizing activity that surpassed conventional hepatitis B-Ig (HBIG) in the HepaRG cell line assay. These results may contribute to the development of effective mAb treatment against HBV infection replacing conventional HBIG administration.
authors.affiliation: Department of Immunology, University of Toyama, Japan. tajikazu@med-u.toyama.ac.jp <tajikazu@med-u.toyama.ac.jp>
authors.forename: Kazuto
authors.initials: K
authors.lastname: Tajiri
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Ozawa
authors.forename: Aishun
authors.initials: A
authors.lastname: Jin
authors.forename: Yoshiharu
authors.initials: Y
authors.lastname: Tokimitsu
authors.forename: Masami
authors.initials: M
authors.lastname: Minemura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishi
authors.forename: Toshiro
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Muraguchi
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000915:Antibody Affinity; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D018604:Epitope Mapping; D006510:Hepatitis B Antibodies / Q000276:immunology*; D006514:Hepatitis B Surface Antigens / Q000276:immunology*; D017325:Hepatitis B Vaccines / Q000276:immunology*; D006515:Hepatitis B virus / Q000276:immunology*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D006510:Hepatitis B Antibodies; D006514:Hepatitis B Surface Antigens; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D007135:Immunoglobulin Variable Region