{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T00:25:30Z","timestamp":1793924730012,"version":"4.8.0"},"posted":{"date-parts":[[2026,7,6]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":47,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T00:00:00Z","timestamp":1783296000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Independent Research Fund Denmark","award":["4308-00112B"],"award-info":[{"award-number":["4308-00112B"]}],"id":[{"id":"https:\/\/ror.org\/05svhj534","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Stavros Niarchos Foundation Institute for Global Infectious Disease Research","id":[{"id":"https:\/\/ror.org\/0210rze73","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Black Family Fund for Translational Medicine at Rockefeller University","id":[{"id":"https:\/\/ror.org\/0420db125","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,7,15]]},"abstract":"<jats:p>Chronic infection with hepatitis B virus (HBV) is characterized by persistent expression of hepatitis B surface antigen (HBsAg), which is associated with profound immune tolerance. Although nucleos(t)ide analogue therapy effectively suppresses viral replication, it neither eliminates HBV nor reverses virus-specific immune dysfunction. Here, we report the results of two parallel first-in-human, dose-escalation studies evaluating a single infusion of mAb19-LS, a long-acting IgG1 monoclonal antibody targeting HBsAg, in individuals with chronic HBV infection receiving nucleos(t)ide analogue therapy. mAb19-LS was generally safe and well tolerated and induced a mean 11-fold increase in antigen clearance. The magnitude and duration of HBsAg suppression were dependent on both baseline antigen levels and mAb19-LS dose, with suppression maintained for more than 36 weeks in individuals receiving the highest dose. Reduction of circulating HBsAg was associated with uptake of HBsAg-IgG immune complexes by monocytes and dendritic cells and inflammatory reprogramming of these antigen-presenting cells. Notably, proliferation of both CD4+ and CD8+ T cells, as well as interferon-\u03b3; and TNF-\u03b1; production in response to HBV antigens, were significantly increased 24 weeks after infusion. Together, these findings demonstrate that mAb19-LS is generally safe and effectively accelerates HBsAg clearance while activating antigen presenting cells and enhancing antiviral T cell responses.<\/jats:p>","DOI":"10.64898\/2026.07.03.26357226","type":"posted-content","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:30:18Z","timestamp":1783355418000},"source":"Crossref","is-referenced-by-count":0,"title":["Anti-HBsAg antibody mAb19-LS enhances antiviral immunity in humans with chronic hepatitis B"],"prefix":"10.64898","author":[{"given":"Zijun","family":"Wang","sequence":"first","affiliation":[{"name":"The Rockefeller University;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary","family":"Tenuta","sequence":"additional","affiliation":[{"name":"The Rockefeller University;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Ngoc Le","sequence":"additional","affiliation":[{"name":"Charite-Universitatsmedizin 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