Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection

Hepatitis B e antigen (HBeAg) is a widely used marker both for chronic hepatitis B (CHB) clinical management and HBV-related basic research. However, due to its high amino acid sequence homology to hepatitis B core antigen (HBcAg), most of available anti-HBe antibodies are cross-reactive with HBcAg...

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Main Authors: Shao-Juan Wang, Zi-Min Chen, Min Wei, Jia-Qi Liu, Zong-Lin Li, Tian-Shu Shi, Sheng Nian, Rao Fu, Yang-Tao Wu, Ya-Li Zhang, Ying-Bin Wang, Tian-Ying Zhang, Jun Zhang, Jun-Hui Xiong, Shu-Ping Tong, Sheng-Xiang Ge, Quan Yuan, Ning-Shao Xia
Format: Article
Language:English
Published: Taylor & Francis Group 2021-01-01
Series:Emerging Microbes and Infections
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Online Access:https://www.tandfonline.com/doi/10.1080/22221751.2020.1862631
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author Shao-Juan Wang
Zi-Min Chen
Min Wei
Jia-Qi Liu
Zong-Lin Li
Tian-Shu Shi
Sheng Nian
Rao Fu
Yang-Tao Wu
Ya-Li Zhang
Ying-Bin Wang
Tian-Ying Zhang
Jun Zhang
Jun-Hui Xiong
Shu-Ping Tong
Sheng-Xiang Ge
Quan Yuan
Ning-Shao Xia
author_facet Shao-Juan Wang
Zi-Min Chen
Min Wei
Jia-Qi Liu
Zong-Lin Li
Tian-Shu Shi
Sheng Nian
Rao Fu
Yang-Tao Wu
Ya-Li Zhang
Ying-Bin Wang
Tian-Ying Zhang
Jun Zhang
Jun-Hui Xiong
Shu-Ping Tong
Sheng-Xiang Ge
Quan Yuan
Ning-Shao Xia
author_sort Shao-Juan Wang
collection DOAJ
description Hepatitis B e antigen (HBeAg) is a widely used marker both for chronic hepatitis B (CHB) clinical management and HBV-related basic research. However, due to its high amino acid sequence homology to hepatitis B core antigen (HBcAg), most of available anti-HBe antibodies are cross-reactive with HBcAg resulting in high interference against accurate measurement of the status and level of HBeAg. In the study, we generated several monoclonal antibodies (mAbs) targeting various epitopes on HBeAg and HBcAg. Among these mAbs, a novel mAb 16D9, which recognizes the SKLCLG (aa −10 to −5) motif on the N-terminal residues of HBeAg that is absent on HBcAg, exhibited excellent detection sensitivity and specificity in pairing with another 14A7 mAb targeting the HBeAg C-terminus (STLPETTVVRRRGR, aa141 to 154). Based on these two mAbs, we developed a novel chemiluminescent HBeAg immunoassay (NTR-HBeAg) which could detect HBeAg derived from various HBV genotypes. In contrast to widely used commercial assays, the NTR-HBeAg completely eliminated the cross-reactivity with secreted HBcAg from precore mutant (G1896A) virus in either cell culture or patient sera. The improved specificity of the NTR-HBeAg assay enables its applicability in cccDNA-targeting drug screening in cell culture systems and also provides an accurate tool for clinical HBeAg detection.
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spelling doaj-art-b4a0b51afac94f5aa4a5cce99d00325f2025-08-20T02:24:43ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512021-01-01101375010.1080/22221751.2020.1862631Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infectionShao-Juan Wang0Zi-Min Chen1Min Wei2Jia-Qi Liu3Zong-Lin Li4Tian-Shu Shi5Sheng Nian6Rao Fu7Yang-Tao Wu8Ya-Li Zhang9Ying-Bin Wang10Tian-Ying Zhang11Jun Zhang12Jun-Hui Xiong13Shu-Ping Tong14Sheng-Xiang Ge15Quan Yuan16Ning-Shao Xia17State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaXiamen Innodx Biotech Co., Ltd., Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaXiamen Innodx Biotech Co., Ltd., Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaNational Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, People’s Republic of ChinaLiver Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USAState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaState Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of ChinaHepatitis B e antigen (HBeAg) is a widely used marker both for chronic hepatitis B (CHB) clinical management and HBV-related basic research. However, due to its high amino acid sequence homology to hepatitis B core antigen (HBcAg), most of available anti-HBe antibodies are cross-reactive with HBcAg resulting in high interference against accurate measurement of the status and level of HBeAg. In the study, we generated several monoclonal antibodies (mAbs) targeting various epitopes on HBeAg and HBcAg. Among these mAbs, a novel mAb 16D9, which recognizes the SKLCLG (aa −10 to −5) motif on the N-terminal residues of HBeAg that is absent on HBcAg, exhibited excellent detection sensitivity and specificity in pairing with another 14A7 mAb targeting the HBeAg C-terminus (STLPETTVVRRRGR, aa141 to 154). Based on these two mAbs, we developed a novel chemiluminescent HBeAg immunoassay (NTR-HBeAg) which could detect HBeAg derived from various HBV genotypes. In contrast to widely used commercial assays, the NTR-HBeAg completely eliminated the cross-reactivity with secreted HBcAg from precore mutant (G1896A) virus in either cell culture or patient sera. The improved specificity of the NTR-HBeAg assay enables its applicability in cccDNA-targeting drug screening in cell culture systems and also provides an accurate tool for clinical HBeAg detection.https://www.tandfonline.com/doi/10.1080/22221751.2020.1862631Hepatitis B virusHepatitis B e antigenmonoclonal antibodycccDNA surrogateimmunoassay
spellingShingle Shao-Juan Wang
Zi-Min Chen
Min Wei
Jia-Qi Liu
Zong-Lin Li
Tian-Shu Shi
Sheng Nian
Rao Fu
Yang-Tao Wu
Ya-Li Zhang
Ying-Bin Wang
Tian-Ying Zhang
Jun Zhang
Jun-Hui Xiong
Shu-Ping Tong
Sheng-Xiang Ge
Quan Yuan
Ning-Shao Xia
Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection
Emerging Microbes and Infections
Hepatitis B virus
Hepatitis B e antigen
monoclonal antibody
cccDNA surrogate
immunoassay
title Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection
title_full Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection
title_fullStr Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection
title_full_unstemmed Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection
title_short Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection
title_sort specific determination of hepatitis b e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis b virus infection
topic Hepatitis B virus
Hepatitis B e antigen
monoclonal antibody
cccDNA surrogate
immunoassay
url https://www.tandfonline.com/doi/10.1080/22221751.2020.1862631
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