HBVZ10 Exhibits Robust In Vivo Potency and Synergizes with Entecavir to Drive Efficient cccDNA Elimination and HBsAg Seroclearance.

Authors

Bai-Hua Zhang, Yuanping Zhou, Yukun Wu, Stephen Horrigan, Laura Luckenbaugh, Jianming Hu, Fabien Zoulim, Yong-Yuan Zhang

Published in

Antiviral research. Pages 106518. Aug 21, 2026. Epub Aug 21, 2026.

Abstract

Current nucleos(t)ide analog (NA) therapies for chronic hepatitis B (CHB) fail to achieve a functional cure because they do not completely halt viral replication, allowing low-level virion release to continuously replenish the intrahepatic covalently closed circular DNA (cccDNA) pool. Emerging siRNA and antisense oligonucleotides (ASO) show promise but typically require baseline HBsAg levels below 1,000 IU/mL to be effective. HBVZ10 is a novel therapeutic candidate designed for endogenous production of neutralizing anti-HBs antibodies using skeletal muscle cells.
We evaluated the in vivo potency of HBVZ10 and efficacy of combination with Entecavir (ETV) in immunodeficient mice with humanized livers. Primary endpoints included serum HBV DNA, HBsAg, and anti-HBs antibody titers, alongside intrahepatic relaxed circular DNA (rcDNA) and cccDNA levels.
Following a single administration, HBVZ10-mediated anti-HBs titers rapidly rose and were maintained at ≥100,000 mIU/mL until termination (231 days). HBVZ10 monotherapy consistently suppressed serum HBV DNA down by 78-93% and HBsAg down by 80-90% over 170 days. The HBVZ10+ETV combination therapy induced HBsAg seroclearance in 88.9% (8/9) of mice, significantly outperforming ETV monotherapy (10%, 1/10; p = 0.001). Furthermore, the combination resulted in a 10-fold and 100-fold greater reduction in hepatic rcDNA and cccDNA, respectively, compared to ETV alone.
HBVZ10 demonstrates robust in vivo potency through reducing massive HBsAg burden and creating the conditions for effectively neutralizing virions and blocking extracellular pathways for cccDNA replenishment. This capacity provides a critical pharmacological foundation for synergy when combined with intracellular inhibitors.

PMID:
42628880
Bibliographic data and abstract were imported from PubMed on 22 Aug 2026.

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