# Inhibition of HBV Replication by a Fully Humanized Neutralizing Antibody In Vivo and In Vitro

## TL;DR

A fully humanized antibody was developed to inhibit HBV replication in both lab and animal models, showing promise for treating hepatitis B.

## Contribution

A fully humanized neutralizing antibody was developed and tested in vivo and in vitro for HBV inhibition.

## Key findings

- The antibody showed dose-dependent reduction in HBsAg and HBV DNA in a mouse model.
- No cytotoxicity was observed in human hepatocytes at tested concentrations.
- The antibody reduced antigen-antibody complexes and slowed CD8+T lymphocyte depletion.

## 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 highdose 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.