{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T21:30:03Z","timestamp":1790371803554,"version":"4.1.0"},"reference-count":45,"publisher":"American Society for Clinical Investigation","issue":"23","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"the National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32300768"],"award-info":[{"award-number":["32300768"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"the Major Program of Guangzhou National Laboratory","award":["GZNL2025C01036"],"award-info":[{"award-number":["GZNL2025C01036"]}]},{"name":"the National Key R&D Program of China","award":["2018ZX10301-404"],"award-info":[{"award-number":["2018ZX10301-404"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,8]]},"abstract":"<jats:p>\n                    Recombinant hepatitis B surface antigen (rHBsAg) vaccine with various adjuvants fails to break T and B cell tolerance in hosts with chronic hepatitis B (CHB). This study aims to explore the mechanisms to break immune tolerance that allows the host to respond to rHBsAg, achieving a cure for CHB. We engineered an anti\u2013PD-L1\u2013IFN-\u03b1 (aPD-L1\u2013IFN-\u03b1) heterodimeric fusion protein to allow rHBsAg to rejuvenate T and B cell responses in hepatitis B virus\u2013tolerant (HBV-tolerant) mice. S.c. coimmunization with aPD-L1\u2013IFN-\u03b1 and rHBsAg significantly enhanced antigen uptake and maturation of both macrophage and dendritic cell (DC) subsets in draining lymph nodes. Macrophages drove early B cell activation, while cDC1s primed CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, breaking tolerance and leading to both B cell and cytotoxic T lymphocyte (CTL) differentiation. This strategy elicited not only anti-HBsAg neutralizing antibodies but also HBsAg-specific CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses, achieving a functional cure without systemic toxicity. The efficacy of the aPD-L1\u2013IFN-\u03b1 adjuvant depended on both PD-L1\n                    <jats:italic>cis<\/jats:italic>\n                    -targeting and IFN-\u03b1 receptor signaling in antigen-presenting cells. These findings establish aPD-L1\u2013IFN-\u03b1 as a translatable adjuvant to break the strong tolerance induced by CHB, providing a dual-pathway strategy to induce HBV-specific T and B cell responses.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.198097","type":"journal-article","created":{"date-parts":[[2025,12,7]],"date-time":"2025-12-07T19:00:36Z","timestamp":1765134036000},"source":"Crossref","is-referenced-by-count":3,"title":["Anti\u2013PD-L1\u2013IFN-\u03b1\u2013adjuvanted HBsAg vaccine overcomes HBV immune tolerance through targeting both DCs and macrophages"],"prefix":"10.1172","volume":"10","author":[{"given":"Chao-Yang","family":"Meng","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Liang","sequence":"additional","affiliation":[{"name":"Center for Cancer Biology, School of 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