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Article

PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B

1
Institute of Virology, School of Medicine, Technical University of Munich/Helmholtz Zentrum München, Trogerstrasse 30, 81675 Munich, Germany
2
German Center for Infection Research (DZIF), Partner Site Munich, 81675 Munich, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to the work.
Biomolecules 2022, 12(3), 470; https://doi.org/10.3390/biom12030470
Submission received: 13 February 2022 / Revised: 11 March 2022 / Accepted: 15 March 2022 / Published: 18 March 2022

Abstract

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.
Keywords: HBV; hepatitis; PD-L1; RNAi; therapeutic vaccination; immunology; checkpoint inhibition HBV; hepatitis; PD-L1; RNAi; therapeutic vaccination; immunology; checkpoint inhibition

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MDPI and ACS Style

Bunse, T.; Kosinska, A.D.; Michler, T.; Protzer, U. PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B. Biomolecules 2022, 12, 470. https://doi.org/10.3390/biom12030470

AMA Style

Bunse T, Kosinska AD, Michler T, Protzer U. PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B. Biomolecules. 2022; 12(3):470. https://doi.org/10.3390/biom12030470

Chicago/Turabian Style

Bunse, Till, Anna D. Kosinska, Thomas Michler, and Ulrike Protzer. 2022. "PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B" Biomolecules 12, no. 3: 470. https://doi.org/10.3390/biom12030470

APA Style

Bunse, T., Kosinska, A. D., Michler, T., & Protzer, U. (2022). PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B. Biomolecules, 12(3), 470. https://doi.org/10.3390/biom12030470

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