A broad-spectrum nanobody targeting the C-terminus of the hepatitis B surface antigen for chronic hepatitis B infection therapy

Yue Wang; Yaxian Mei; Zhenghong Ao; Yuanzhi Chen; Yichao Jiang; Xiaoqing Chen; Ruoyao Qi; Baorong Fu; Jixian Tang; Mujin Fang; Min You; Tianying Zhang; Quan Yuan; Wenxin Luo; Ningshao Xia

doi:10.1016/j.antiviral.2022.105265

A broad-spectrum nanobody targeting the C-terminus of the hepatitis B surface antigen for chronic hepatitis B infection therapy

Antiviral Res. 2022 Mar:199:105265. doi: 10.1016/j.antiviral.2022.105265. Epub 2022 Feb 17.

Authors

Affiliations

¹ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Science, Xiamen University, Xiamen, 361105, China.
² State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Science, Xiamen University, Xiamen, 361105, China. Electronic address: yuanquan@xum.edu.cn.
³ State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Public Health, School of Life Science, Xiamen University, Xiamen, 361105, China. Electronic address: wxluo@xmu.edu.cn.

PMID: 35183645
DOI: 10.1016/j.antiviral.2022.105265

Abstract

Sustainable viral suppression with hepatitis B surface antigen (HBsAg) loss is the new treatment goal for chronic hepatitis B (CHB). The role of antibodies in therapies for persistent hepatitis B virus (HBV) infection has received constant attention. While immunotherapy holds great promise, challenges for the antibody-based prevention and control of HBV in CHB include broad HBV antigenic diversity and the need for long-term viral suppression. In this study, we identified a new anti-HBsAg nanobody (Nb), 125s, isolated from HBsAg-immunized alpaca and confirmed its excellent potency in HBsAg clearance and broad-spectrum therapeutic activity against three HBV subtypes in vivo. In addition, we characterized a novel epitope at the C-terminus of the HBsAg surface motif from amino acids 157 to 174. A 125s-based long-term passive immunization program was efficacious at HBsAg clearance and inducing cellular immune responses, offering a promising outlook for CHB immunotherapy.

Keywords: Broad-spectrum therapeutic antibody; Chronic hepatitis B virus; Epitope mapping; Heavy chain antibody; Hepatitis B surface Antigen; Immunotherapy.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

DNA, Viral
Hepatitis B Antibodies
Hepatitis B Surface Antigens
Hepatitis B virus / genetics
Hepatitis B*
Hepatitis B, Chronic* / drug therapy
Humans

Substances

DNA, Viral
Hepatitis B Antibodies
Hepatitis B Surface Antigens