Defining the specificity and function of a human neutralizing antibody for Hepatitis B virus
Saket Jhajharia 1 , Fritz Lai 1 2 , Heng Boon Low 1 , Kiren Purushotorman 3 , Bhuvaneshwari D/O Shunmuganathan 3 , Conrad En Zuo Chan 4 , Rachel Hammond 5 , Hans-Jürgen Netter 5 , Qingfeng Chen 1 2 , Seng Gee Lim 6 , Paul A MacAry 7 8
Affiliations
Affiliations
1
Department of Medicine, National University of Singapore, Singapore, Singapore.
2
Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), Singapore, Singapore.
3
Life Sciences Institute, National University of Singapore, Singapore, Singapore.
4
Biological Defence Programme, DSO National Laboratories, Singapore, Singapore.
5
Victorian Infectious Diseases Reference Laboratory (VIDRL), Melbourne Health, The Peter Doherty Institute, Melbourne, VIC, Australia.
6
National University Hospital, Division of Gastroenterology and Hepatology, Singapore, Singapore. [email protected].
7
Department of Medicine, National University of Singapore, Singapore, Singapore. [email protected].
8
Life Sciences Institute, National University of Singapore, Singapore, Singapore. [email protected].
PMID: 36271019 DOI: 10.1038/s41541-022-00516-7
Abstract
Hepatitis B Virus (HBV) is a hepadnavirus that is the principal pathogen underlying viral liver disease in human populations. In this study, we describe the isolation and characterization of a fully human monoclonal antibody for HBV. This HuMab was isolated by a combinatorial screen of the memory B-cell repertoire from an acute/recovered HBV-infected patient. Lead candidate selection was based upon strong binding and neutralizing activity for live HBV. We provide a detailed biochemical/biophysical, and subclass characterization of its specificity and affinity against all of the principal HBV genotypes combined with a functional analysis of its in vitro activity. We also demonstrate its potential as a prophylaxis/therapy in vivo using human liver chimeric mouse models for HBV infection. These data have important implications for our understanding of natural human immunity to HBV and suggest that this potentially represents a new antibody-based anti-viral candidate for prophylaxis and/or therapy for HBV infection.