{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:30:06Z","timestamp":1790371806257,"version":"4.1.0"},"reference-count":43,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Prevalence of chronic hepatitis B virus (HBV) infection remains a major global health issue. Research into a cure has focused on finite combinatorial interventions that aim to reduce HBV surface antigen (HBsAg), suppress virus specific immune tolerance, and induce an adaptive response that functionally controls the virus.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In C57BL\/6 mice transduced with adeno-associated virus encoding the HBV genome, which replicate HBV and persistently express HBsAg at 10<jats:sup>4<\/jats:sup> IU\/mL or higher, a combination of small interfering RNA (siRNA) knockdown of HBsAg expression followed by immunization with a self amplifying RNA therapeutic HBV vaccine failed to establish HBV control. Using this <jats:italic>in vivo<\/jats:italic> murine model, we screened for immunomodulatory agents added after HBV siRNA knockdown, and in combination with therapeutic vaccination, that may enhance the HBV adaptive immune response to control HBV. <\/jats:p><\/jats:sec><jats:sec><jats:title>Results\/Discussion<\/jats:title><jats:p>In mice with very high levels of HBsAg (10<jats:sup>4<\/jats:sup>\u201310<jats:sup>5<\/jats:sup> IU\/mL), levels that are observed clinically during standard HBV therapy and that were brought low (10<jats:sup>2<\/jats:sup> IU\/mL) by HBV siRNA pre-treatment prior to therapeutic vaccination, PDL1 blockade in combination with stabilized cytokines IL-2 or IL-15 led to immune control of HBsAg in vaccinated animals.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1562107","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T04:12:11Z","timestamp":1752639131000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["IL-2 and IL-15 augment HBV therapeutic vaccination and PD1 blockade for functional cure in the AAV-HBV mouse model"],"prefix":"10.3389","volume":"16","author":[{"given":"Gavin","family":"Lewis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Malo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Rowland","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenaya","family":"Hooks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao 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