1
Institute for Advanced Co-Creation Studies,Research, Institute for Microbial Diseases, Osaka University, Osaka, Japan.
2
Department of Applied Chemistry and Bioengineering, Graduate School of Engineering, Osaka City University, Osaka, Japan.
3
Department of Microbiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.
4
Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, Osaka University, Osaka, Japan.
5
The Research Center for Hepatitis and Immunology, National Center for Global Health and Medicine, Chiba, Japan.
6
Department of Microbiology, Yokohama City University Graduate School of Medicine, Kanagawa, Japan.
7
Bio Matrix Research, Inc, Chiba, Japan.
8
Genome Medical Science Project, National Center for Global Health and Medicine, Ichikawa, Japan.
9
Center for Infectious Disease Education and Research, Osaka University, Osaka, Japan.
10
Laboratory of Viral Control, Research Institute for Microbial Diseases, Osaka University, Osaka, Japan.
PMID: 35084739 DOI: 10.1111/1348-0421.12964
Abstract
Antibodies against hepatitis B virus S protein can protect against hepatitis B virus (HBV) infection. Therefore, hepatitis B immunoglobulin (HBIG), which contains HBsAb, is used clinically as a therapy for HBV infection. In this study, we obtained a series of monoclonal antibodies that recognize multiple HBV genotypes. All the antibodies recognized conformational epitopes of S protein, but not linear epitopes. Several antibodies neutralized HBV infection and exhibited strong affinities and neutralizing activities. Antigenic epitope analysis demonstrated that they recognized residue Ile152 of S protein, which is localized outside the "a" determinant. Ile152 is highly conserved, and a mutation in this residue resulted in reduced expression of large hepatitis B surface proteins (L protein), suggesting that the amino acid at this position is involved in the expression of L protein. In addition, the antibodies neutralized the infection of hepatitis D virus possessing a Gly145 mutation to Arg in S protein, which is a well-known escape mutation against HBIG treatment. Using mouse monoclonal antibodies, we successfully established a humanized antibody possessing affinities and neutralizing activities similar to those of the original mouse antibody. The antibodies generated in this study may have potential for use in alternative antibody therapies for HBV infection. This article is protected by copyright. All rights reserved.
Keywords: hepatitis B virus; hepatitis D virus; humanized antibody; monoclonal antibody; neutralizing antibody.
This article is protected by copyright. All rights reserved.