GUT. 2022 Dec 13
Chao-Yang Meng, Shiyu Sun, Yong Liang, Hairong Xu
Products used in the paper Details Operation
(AAV)-HBV1.3 virus The adeno-associated virus (AAV)-HBV1.3 virus was purchased from PackGene Biotech (Guangzhou, China). This recombinant virus carries 1.3 copies of the HBV genome (genotype D, serotype ayw) and is packaged in AAV serotype 8 capsids. Request Quote

Research Field: HBV

AAV Serotype: AAV8

Dose: C57BL/6J mice were injected with the AAV-HBV1.3 virus through the tail vein (1×10^11 viral genome copies per mouse). After 5 weeks or more, stable HBV carrier mice (serum HBsAg >1000 IU/mL) were used. Blood was collected from the retro-orbital sinuses at the indicated time points in the indicated experiments to monitor the levels of HBsAg, hepatitis B e antigen (HBeAg), ayw subtype-specific anti-HBsAg antibodies and HBV-DNA in the serum.

Routes of Administration: tail vein

Animal or cell line strain: C57BL/6J mice


Objective The purpose of this study is to develop an anti-PDL1-based interferon (IFN) fusion protein to overcome the chronic hepatitis B virus (HBV)-induced immune tolerance, and combine this immunotherapy with a HBV vaccine to achieve the functional cure of chronic hepatitis B (CHB) infection.

Design We designed an anti-PDL1-IFNα heterodimeric fusion protein, in which one arm was derived from anti-PDL1 antibody and the other arm was IFNα, to allow targeted delivery of IFNα into the liver by anti-PDL1 antibody. The effect of the anti-PDL1-IFNα heterodimer on overcoming hepatitis B surface antigen (HBsAg) vaccine resistance was evaluated in chronic HBV carrier mice.

Results The anti-PDL1-IFNα heterodimer preferentially targeted the liver and resulted in viral suppression, the PD1/PDL1 immune checkpoint blockade and dendritic cell activation/antigen presentation to activate HBsAg-specific T cells, thus breaking immune tolerance in chronic HBV carrier mice. When an HBsAg vaccine was administered soon after anti-PDL1-IFNα heterodimer treatment, we observed strong anti-HBsAg antibody and HBsAg-specific T cell responses for efficient HBsAg clearance in chronic HBV carrier mice that received the combination treatment but not in those that received either single treatment.

Conclusions Targeting the liver with an engineered anti-PDL1-IFNα heterodimer can break HBV-induced immune tolerance to an HBsAg vaccine, offering a promising translatable therapeutic strategy for the functional cure of CHB.

Popular Services

AAV Packaging Service

AAV Analytical Service

Vector Design