Inhibition of HBV replication by a fully humanized neutralizing antibody in vivo and in vitro
Year: 2025
Type: article
Abstract: Neutralizing antibodies are capable of specifically binding to the HBsAg virus, thereby preventing HBV infection and subsequently reducing viral antigen load in both the liver and systemic circulation. This has significant implications for restoring the postnatal immune function. By utilizing the phage antibody library technology, we successfully screened a fully humanized neutralizing antibody targeting the hepatitis B surface antigen. The antiviral activity was assessed in primary human hepatocytes (PHHs) by determining the EC50 values for HBeAg and HBsAg biomarkers in HBV types B, C, and D; no cytotoxicity was observed within the tested concentration range. Furthermore, HT-102 exhibited no ADCC effect but displayed a weak CDC effect along with a dose-dependent response. We established an AAV/HBV mouse model and observed significant dose-dependent reduction in HBsAg and HBV DNA levels for both the medium-dose and high-dose groups. The immunohistochemical staining data showed dose-dependent reduction in HBsAg expression in the liver, with high-dose group exhibiting minimal positive expression. Finally, a mild immune response was induced, while reducing the burden of antigen–antibody complexes circulating within the system. Consequently, strain on the patient’s immune system was alleviated by effectively slowing down CD8+T lymphocyte depletion, and functional cure was ultimately achieved as intended.
Source: Acta Naturae
Authors: Zhipeng Zhang, Yanqin Ma, Yan He, Dong Wang, Huaien Song, Kun Yue, Xiaomei Zhang
Institution: Jiangnan University
Language: English
Topic: Hepatitis B Virus Studies
Subfield: Epidemiology
Field: Medicine
Domain: Health Sciences
Open Access status: diamond
OpenAlex ID: W4409734353