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

Shu-Ping Tong¹  Jun-Hui Xiong²  Ying-Bin Wang³  Min Wei³  Zong-Lin Li³  Ya-Li Zhang³  Tian-Shu Shi³  Jun Zhang³  Sheng Nian³  Sheng-Xiang Ge³  Shao-Juan Wang³  Ning-Shao Xia³  Yang-Tao Wu³  Quan Yuan³  Rao Fu³  Tian-Ying Zhang³  Zi-Min Chen⁴  Jia-Qi Liu⁴ 

[1] Liver Research Center, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, RI, USA;National Institute of Diagnostics and Vaccine Development in Infectious Diseases, School of Life Science, Xiamen University, Xiamen, People’s Republic of China;State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, School of Public Health, Xiamen University, Xiamen, People’s Republic of China;Xiamen Innodx Biotech Co., Ltd., Xiamen, People’s Republic of China;

关键词: Hepatitis B virus;    Hepatitis B e antigen;    monoclonal antibody;    cccDNA surrogate;    immunoassay;   

DOI  :  10.1080/22221751.2020.1862631

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown