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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)

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	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

Corresponding Author

Keywords Checkpoint ; Hepatitis ; Immunology ; Inhibition Hbv ; Pd-l1 ; Rnai ; Therapeutic Vaccination

ISSN (print) / ISBN 2218-273X

e-ISSN 2218-273X

Journal Biomolecules

Quellenangaben Volume: 12, Issue: 3, Article Number: 470

Publisher MDPI

Publishing Place Basel

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute of Virology (VIRO)

Grants German Center for Infection Research
European Union
Deutsche Forschungsgemeinschaft