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Bunse, T. ; Kosinska, A. ; Michler, T. ; Protzer, U.

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

Biomolecules 12:470 (2022)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Checkpoint ; Hepatitis ; Immunology ; Inhibition Hbv ; Pd-l1 ; Rnai ; Therapeutic Vaccination
ISSN (print) / ISBN 2218-273X
e-ISSN 2218-273X
Zeitschrift Biomolecules
Quellenangaben Band: 12, Heft: 3, Seiten: , Artikelnummer: 470 Supplement: ,
Verlag MDPI
Verlagsort Basel
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)
Förderungen German Center for Infection Research
European Union
Deutsche Forschungsgemeinschaft