确定人乙型肝炎病毒中和抗体的特异性和功能

StephenW

确定人乙型肝炎病毒中和抗体的特异性和功能
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 , 保罗 A MacAry 7 8
隶属关系
隶属关系

    1
    新加坡国立大学医学系，新加坡，新加坡。
    2
    新加坡科学、技术和研究机构 (A*STAR) 分子和细胞生物学研究所。
    3
    新加坡国立大学生命科学研究所，新加坡，新加坡。
    4
    生物防御计划，DSO 国家实验室，新加坡，新加坡。
    5
    维多利亚传染病参考实验室 (VIDRL)，墨尔本健康，彼得多尔蒂研究所，墨尔本，维多利亚州，澳大利亚。
    6
    新加坡国立大学医院胃肠病学和肝病学部。 [email protected]。
    7
    新加坡国立大学医学系，新加坡，新加坡。 [email protected]。
    8
    新加坡国立大学生命科学研究所，新加坡，新加坡。 [email protected]。

    PMID：36271019 DOI：10.1038/s41541-022-00516-7

抽象的

乙型肝炎病毒 (HBV) 是一种肝炎病毒，是人群中病毒性肝病的主要病原体。在本研究中，我们描述了针对 HBV 的全人源单克隆抗体的分离和表征。该 HuMab 是通过对急性/康复的 HBV 感染患者的记忆 B 细胞库的组合筛选分离出来的。主要候选者的选择基于对活 HBV 的强结合和中和活性。我们提供了详细的生化/生物物理，以及其对所有主要 HBV 基因型的特异性和亲和力的亚类表征，并结合对其体外活性的功能分析。我们还使用人类肝脏嵌合小鼠模型证明了其作为体内预防/治疗HBV感染的潜力。这些数据对我们理解人类对 HBV 的自然免疫具有重要意义，并表明这可能代表了一种新的基于抗体的抗病毒候选药物，用于预防和/或治疗 HBV 感染。

© 2022。作者。

StephenW

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.

© 2022. The Author(s).

StephenW

https://www.nature.com/articles/s41541-022-00516-7.pdf