J Microbiol Biotechnol. 2018 Aug 28;28(8):1376-1383. doi: 10.4014/jmb.1803.03056.
Generation and Characterization of a Neutralizing Human Monoclonal Antibody to Hepatitis B Virus PreS1 from a Phage-Displayed Human Synthetic Fab Library.
Jo G1, Jeong MS1, Wi J2, Kim DH3, Kim S1, Kim D1, Yoon JY1, Chae H1, Kim KH3,4, Hong HJ1,2.
Author information
1
Department of Systems Immunology, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea.
2
Scripps Korea Antibody Institute, Chuncheon 24341, Republic of Korea.
3
Department of Pharmacology, Center for Cancer Research and Diagnostic Medicine, IBST, School of Medicine, Konkuk University, Seoul 05029, Republic of Korea.
4
Research Institute of Medical Sciences, Konkuk University, Seoul 05029, Republic of Korea.
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 (KD) 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:
Hepatitis B virus; human monoclonal antibody; neutralizing antibody; phage display; preS1; synthetic antibody library