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PD-L1 silencing in liver using siRNAs enhances efficacy of therapeutic vaccination for chronic hepatitis B.

Biomolecules 12:470 (2022)
Publ. Version/Full Text DOI PMC
Open Access Gold
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In chronic hepatitis B virus (HBV) infection, virus-specific T cells are scarce and partially dysfunctional. Therapeutic vaccination is a promising strategy to induce and activate new virus-specific T cells. In long-term or high-level HBV carriers, however, therapeutic vaccination by itself may not suffice to cure HBV. One reason is the impairment of antiviral T cells by immune checkpoints. In this study, we used small-interfering RNA (siRNA) in combination with a heterologous prime-boost therapeutic vaccination scheme (TherVacB) to interfere with a major immune checkpoint, the interaction of programmed death protein-1 (PD-1) and its ligand (PDL-1). In mice persistently replicating HBV after infection with an adeno-associated virus harboring the HBV genome, siRNA targeting PD-L1 resulted in a higher functionality of HBV-specific CD8+ T cells after therapeutic vaccination, and allowed for a more sustained antiviral effect and control of HBV in peripheral blood and in the liver. The antiviral effect was more pronounced if PD-L1 was down-regulated during prime than during boost vaccination. Thus, targeting PD-L1 using siRNA is a promising approach to enhance the efficacy of therapeutic vaccination and finally cure HBV.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Checkpoint ; Hepatitis ; Immunology ; Inhibition Hbv ; Pd-l1 ; Rnai ; Therapeutic Vaccination
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 2218-273X
e-ISSN 2218-273X
Journal Biomolecules
Quellenangaben Volume: 12, Issue: 3, Pages: , Article Number: 470 Supplement: ,
Publisher MDPI
Publishing Place Basel
Reviewing status Peer reviewed
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-502700-003
Grants German Center for Infection Research
European Union
Deutsche Forschungsgemeinschaft
Scopus ID 85126645384
PubMed ID 35327662
Erfassungsdatum 2022-07-21