{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:36:57Z","timestamp":1790753817441,"version":"4.1.0"},"reference-count":23,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,18]],"date-time":"2022-03-18T00:00:00Z","timestamp":1647561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB-TRR 179\/2 2020 \u2013272983813, project TP18"],"award-info":[{"award-number":["SFB-TRR 179\/2 2020 \u2013272983813, project TP18"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","award":["Horizon 2020, grant agreement no. 848223 (TherVacB consortium)"],"award-info":[{"award-number":["Horizon 2020, grant agreement no. 848223 (TherVacB consortium)"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"German Center for Infection Research","doi-asserted-by":"publisher","award":["Individual stipends to Till Bunse and Thomas Michler via the DZIF Academy"],"award-info":[{"award-number":["Individual stipends to Till Bunse and Thomas Michler via the DZIF Academy"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/biom12030470","type":"journal-article","created":{"date-parts":[[2022,3,20]],"date-time":"2022-03-20T21:25:00Z","timestamp":1647811500000},"page":"470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["PD-L1 Silencing in Liver Using siRNAs Enhances Efficacy of Therapeutic Vaccination for Chronic Hepatitis B"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2175-7008","authenticated-orcid":false,"given":"Till","family":"Bunse","sequence":"first","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, Trogerstrasse 30, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna D.","family":"Kosinska","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, Trogerstrasse 30, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4174-3316","authenticated-orcid":false,"given":"Thomas","family":"Michler","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, Trogerstrasse 30, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9421-1911","authenticated-orcid":false,"given":"Ulrike","family":"Protzer","sequence":"additional","affiliation":[{"name":"Institute of Virology, School of Medicine, Technical University of Munich\/Helmholtz Zentrum M\u00fcnchen, Trogerstrasse 30, 81675 Munich, Germany"},{"name":"German Center for Infection Research (DZIF), Partner Site Munich, 81675 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,18]]},"reference":[{"key":"ref_1","unstructured":"WHO (2022, January 18). 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