{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T06:57:07Z","timestamp":1776236227288,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T00:00:00Z","timestamp":1775347200000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T00:00:00Z","timestamp":1775001600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["YFC2311001"],"award-info":[{"award-number":["YFC2311001"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010905","name":"Major Research Plan","doi-asserted-by":"publisher","award":["81991492"],"award-info":[{"award-number":["81991492"]}],"id":[{"id":"10.13039\/501100010905","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82041039"],"award-info":[{"award-number":["82041039"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82372237"],"award-info":[{"award-number":["82372237"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MedComm"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Chronic hepatitis B (CHB) remains incurable due to the immune system's tolerance toward the hepatitis B virus (HBV) surface antigen (HBsAg). This study aimed to achieve a functional cure by breaking HBV tolerance through immunotherapy. CHB patients were treated with either standard nucleotide analog (NA) therapy (Adefovir Dipivoxil, ADV) (Cohort 1) or ADV combined with interferon\u2010alpha (IFN\u2010\u03b1) (Cohort 2). Additionally, a third cohort received the THRIL\u2010GM\u2010Vac regimen: three low\u2010dose GM\u2010CSF injections followed by one dose of the HBV vaccine, alongside standard treatment. THRIL\u2010GM\u2010Vac treatment (Cohort 3) achieved a significant 2log10 reduction in HBsAg levels in 21.7% of participants, and 8.7% HBsAg clearance in Cohort 3 compared to 0% and 4.17% in Cohorts 1 and 2, respectively. Furthermore, THRIL\u2010GM\u2010Vac significantly reduced HBV\u2010specific tolerogenic T cells (Tregs), explaining the sustained HBsAg decrease. Upregulation of anti\u2010HBV T cell responses confirmed THRIL\u2010GM\u2010Vac's ability to disrupt HBV tolerance and enhance HBsAg\u2010specific cellular immunity. This suggests its potential effectiveness in treating individuals with moderate to low HBsAg levels. THRIL\u2010GM\u2010Vac treatment in Cohort 3 resulted in 8.7% HBsAg clearance alongside Treg depletion and enhanced anti\u2010viral T cell responses. These findings present a promising strategy to overcome immunotolerance and potentially combat chronic HBV infection.<\/jats:p>","DOI":"10.1002\/mco2.70676","type":"journal-article","created":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T16:25:33Z","timestamp":1775406333000},"source":"Crossref","is-referenced-by-count":0,"title":["Overcoming Immunotolerance in Chronic Hepatitis B: Efficacy of Granulocyte\u2010Macrophage Colony\u2010Stimulating Factor\u2013Based Immunotherapy in Achieving Hepatitis B Surface Antigen Seroclearance"],"prefix":"10.1002","volume":"7","author":[{"given":"Shuang","family":"Geng","sequence":"first","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS) College of Basic Medical Sciences Fudan University Shanghai China"},{"name":"Cumming School of Medicine University of Calgary  Calgary Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Feifei","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Infectious Disease and Biosecurity Fudan University Shanghai China"},{"name":"National Medical Center for Infectious Diseases Huashan Hospital Fudan University Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyu","family":"Jia","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease the First Affiliated Hospital Zhejiang University  Hangzhou Zhejiang Province China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Medical Molecular Virology (MOE\/NHC\/CAMS) College of Basic Medical Sciences Fudan University Shanghai China"},{"name":"Advaccine Biopharmaceutics (Suzhou) Co. 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