Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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Generation and Characterization of a Neutralizing Human Monoclonal Antibody to Hepatitis B Virus PreS1 from a Phage-Displayed Human Synthetic Fab Library

  • Jo, Gyunghee (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Jeong, Mun Sik (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Wi, Jimin (Scripps Korea Antibody Institute) ;
  • Kim, Doo Hyun (Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University) ;
  • Kim, Sangkyu (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Kim, Dain (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Yoon, Jun-Yeol (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Chae, Heesu (Department of Systems Immunology, College of Biomedical Science, Kangwon National University) ;
  • Kim, Kyun-Hwan (Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University) ;
  • Hong, Hyo Jeong (Department of Systems Immunology, College of Biomedical Science, Kangwon National University)
  • Received : 2018.04.16
  • Accepted : 2018.05.23
  • Published : 2018.08.28
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Abstract

The hepatitis B virus (HBV) envelope contains small (S), middle (M), and large (L) proteins. PreS1 of the L protein contains a receptor-binding motif crucial for HBV infection. This motif is highly conserved among 10 HBV genotypes (A-J), making it a potential target for the prevention of HBV infection. In this study, we successfully generated a neutralizing human monoclonal antibody (mAb), 1A8 (IgG1), that recognizes the receptor-binding motif of preS1 using a phage-displayed human synthetic Fab library. Analysis of the antigen-binding activity of 1A8 for different genotypes indicated that it can specifically bind to the preS1 of major HBV genotypes (A-D). Based on Bio-Layer interferometry, the affinity ($K_D$) of 1A8 for the preS1 of genotype C was 3.55 nM. 1A8 immunoprecipitated the hepatitis B virions of genotypes C and D. In an in vitro neutralization assay using HepG2 cells overexpressing the cellular receptor sodium taurocholate cotransporting polypeptide, 1A8 effectively neutralized HBV infection with genotype D. Taken together, the results suggest that 1A8 may neutralize the four HBV genotypes. Considering that genotypes A-D are most prevalent, 1A8 may be a neutralizing human mAb with promising potential in the prevention and treatment of HBV infection.

Keywords

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