Specific determination of hepatitis B e antigen by antibodies targeting precore unique epitope facilitates clinical diagnosis and drug evaluation against hepatitis B virus infection
| Autor: | Junhui Xiong, Ningshao Xia, Yangtao Wu, Tianying Zhang, Rao Fu, Sheng Nian, Zonglin Li, Shuping Tong, Shengxiang Ge, Yali Zhang, Min Wei, Tian-Shu Shi, Chen Zimin, Yingbin Wang, Quan Yuan, Jia-Qi Liu, Jun Zhang, Shaojuan Wang |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Epidemiology viruses Amino Acid Motifs Cell Culture Techniques medicine.disease_cause Epitope Epitopes Drug Discovery Hepatitis B e Antigens media_common medicine.diagnostic_test biology Antibodies Monoclonal virus diseases Hep G2 Cells General Medicine Hepatitis B Core Antigens Infectious Diseases HBeAg Antibody Research Article Hepatitis b e antigen Drug Hepatitis B virus Genotype medicine.drug_class media_common.quotation_subject 030106 microbiology Immunology Monoclonal antibody Microbiology Cell Line 03 medical and health sciences Hepatitis B Chronic Virology medicine Humans immunoassay Hepatitis B Antibodies cccDNA surrogate Hepatitis B e antigen business.industry digestive system diseases 030104 developmental biology monoclonal antibody Immunoassay Luminescent Measurements biology.protein Parasitology business |
| Zdroj: | Emerging Microbes & Infections article-version (VoR) Version of Record |
| ISSN: | 2222-1751 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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