HBsAg and TLR7/8 dual-targeting antibody-drug conjugates induce sustained anti-HBV activity in AAV/HBV mice: a preliminary study
Brief intro:
- Author: Xinya Ye, Xiaoqing Chen, Han Liu, Yichao Jiang, Chengyu Yang, Tao Xu, Ziyou Chen, Yalin Wang, Fentian Chen, Xue Liu, Hai Yu, Quan Yuan, Ningshao Xia, Yuanzhi Chen, Wenxin Luo
- Journal: Antibody Therapeutics
- Doi: https://www.doi.org/10.1093/abt/tbae016
- Publication Date: 2024 Jul 3
Products/Services used in the paper
Quotation shows PackGene:The adeno-associated virus (AAV)-HBV1.3, encapsulating 1.3 copies of the HBV genome (genotype B, serotype adw) in AAV serotype 8 capsids, was acquired from PackGene Biotech (Guangzhou, China).
Research Field:anti-HBV activity
AAV Serotype:AAV8
Targeted organ:liver
Animal or cell line strain:mice
Abstract
Hepatitis B virus (HBV) infection is a significant global health concern due to elevated immunosuppressive viral antigen levels, the host immune system’s inability to manage HBV, and the liver’s immunosuppressive conditions. While immunotherapies utilizing broadly reactive HBV neutralizing antibodies present potential due to their antiviral capabilities and Fc-dependent vaccinal effects, they necessitate prolonged and frequent dosing to achieve optimal therapeutic outcomes. Toll-like receptor 7/8 (TLR7/8) agonists have been demonstrated promise for the cure of chronic hepatitis B, but their systemic use often leads to intense side effects. In this study, we introduced immune-stimulating antibody conjugates which consist of TLR7/8 agonists 1-[[4-(aminomethyl)phenyl]methyl]-2-butyl-imidazo[4,5-c]quinolin-4-amine (IMDQ) linked to an anti-hepatitis B surface antigen (HBsAg) antibody 129G1, and designated as 129G1-IMDQ. Our preliminary study highlights that 129G1-IMDQ can prompt robust and sustained anti-HBsAg specific reactions with short-term administration. This underscores the conjugate’s potential as an effective strategy for HBsAg clearance and seroconversion, offering a fresh perspective for a practical therapeutic approach in the functional cure of CHB.
About PackGene
PackGene Biotech is a world-leading CRO and CDMO, excelling in AAV vectors, mRNA, plasmid DNA, and lentiviral vector solutions. Our comprehensive offerings span from vector design and construction to AAV, lentivirus, and mRNA services. With a sharp focus on early-stage drug discovery, preclinical development, and cell and gene therapy trials, we deliver cost-effective, dependable, and scalable production solutions. Leveraging our groundbreaking π-alpha 293 AAV high-yield platform, we amplify AAV production by up to 10-fold, yielding up to 1e+17vg per batch to meet diverse commercial and clinical project needs. Moreover, our tailored mRNA and LNP products and services cater to every stage of drug and vaccine development, from research to GMP production, providing a seamless, end-to-end solution.
