PMID- 20412816 OWN - NLM STAT- MEDLINE DCOM- 20100914 LR - 20100607 IS - 1872-9096 (Electronic) IS - 0166-3542 (Linking) VI - 87 IP - 1 DP - 2010 Jul TI - Analysis of the epitope and neutralizing capacity of human monoclonal antibodies induced by hepatitis B vaccine. PG - 40-9 LID - 10.1016/j.antiviral.2010.04.006 [doi] AB - 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. CI - 2010 Elsevier B.V. All rights reserved. FAU - Tajiri, Kazuto AU - Tajiri K AD - Department of Immunology, University of Toyama, Japan. tajikazu@med-u.toyama.ac.jp FAU - Ozawa, Tatsuhiko AU - Ozawa T FAU - Jin, Aishun AU - Jin A FAU - Tokimitsu, Yoshiharu AU - Tokimitsu Y FAU - Minemura, Masami AU - Minemura M FAU - Kishi, Hiroyuki AU - Kishi H FAU - Sugiyama, Toshiro AU - Sugiyama T FAU - Muraguchi, Atsushi AU - Muraguchi A LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100420 PL - Netherlands TA - Antiviral Res JT - Antiviral research JID - 8109699 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antibodies, Neutralizing) RN - 0 (Hepatitis B Antibodies) RN - 0 (Hepatitis B Surface Antigens) RN - 0 (Hepatitis B Vaccines) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin Variable Region) SB - IM MH - Adult MH - Antibodies, Monoclonal/*immunology MH - Antibodies, Neutralizing/*immunology MH - Antibody Affinity MH - B-Lymphocytes/immunology MH - Base Sequence MH - Cell Line MH - *Epitope Mapping MH - Hepatitis B Antibodies/*immunology MH - Hepatitis B Surface Antigens/*immunology MH - Hepatitis B Vaccines/*immunology MH - Hepatitis B virus/*immunology MH - Hepatocytes/virology MH - Humans MH - Immunoglobulin G/immunology MH - Immunoglobulin Variable Region/genetics MH - Male MH - Middle Aged MH - Molecular Sequence Data EDAT- 2010/04/24 06:00 MHDA- 2010/09/15 06:00 CRDT- 2010/04/24 06:00 PHST- 2010/02/22 00:00 [received] PHST- 2010/03/30 00:00 [revised] PHST- 2010/04/14 00:00 [accepted] PHST- 2010/04/24 06:00 [entrez] PHST- 2010/04/24 06:00 [pubmed] PHST- 2010/09/15 06:00 [medline] AID - S0166-3542(10)00576-0 [pii] AID - 10.1016/j.antiviral.2010.04.006 [doi] PST - ppublish SO - Antiviral Res. 2010 Jul;87(1):40-9. doi: 10.1016/j.antiviral.2010.04.006. Epub 2010 Apr 20.