Establishment of monoclonal antibodies broadly neutralize infection of hepatitis B virus.
hepatitis B virus
hepatitis D virus
humanized antibody
neutralizing antibody
Journal
Microbiology and immunology
ISSN: 1348-0421
Titre abrégé: Microbiol Immunol
Pays: Australia
ID NLM: 7703966
Informations de publication
Date de publication:
Apr 2022
Apr 2022
Historique:
revised:
23
01
2022
received:
18
01
2022
accepted:
24
01
2022
pubmed:
28
1
2022
medline:
6
4
2022
entrez:
27
1
2022
Statut:
ppublish
Résumé
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, a series of monoclonal antibodies that recognize multiple HBV genotypes was obtained. 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, a humanized antibody possessing affinities and neutralizing activities similar to those of the original mouse antibody was successfully established. The antibodies generated in this study may have the potential for use in alternative antibody therapies for HBV infection.
Identifiants
pubmed: 35084739
doi: 10.1111/1348-0421.12964
doi:
Substances chimiques
Antibodies, Monoclonal
0
Antibodies, Neutralizing
0
Hepatitis B Antibodies
0
Hepatitis B Surface Antigens
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
179-192Subventions
Organisme : Japan Agency for Medical Research and Development
ID : JP21fk0310103h
Organisme : Japan Agency for Medical Research and Development
ID : JP21fk0310105h
Organisme : Japan Agency for Medical Research and Development
ID : JP21fk0310106h
Organisme : Ministry of Education, Culture, Sports, Science, and Technology of Japan
ID : JP20H03495
Informations de copyright
© 2022 The Societies and John Wiley & Sons Australia, Ltd.
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