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Antibody\u2010based regimens have demonstrated potency regarding virus neutralization and HBsAg clearance. However, high dosages or frequent dosing are required for virologic control. In this study, a dual\u2010domain\u2010engineered anti\u2010hepatitis B virus (HBV) therapeutic antibody 73\u2010DY is developed that exhibits significantly improved efficacy regarding both serum and intrahepatic viral clearance. In HBV\u2010tolerant mice, administration of a single dose of 73\u2010DY at 2\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    is sufficient to reduce serum HBsAg by over 3 log\n                    <jats:sub>10<\/jats:sub>\n                    IU mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    and suppress HBsAg to &lt; 100 IU mL\n                    <jats:sup>\u22121<\/jats:sup>\n                    for two weeks, demonstrating a dose\u2010lowering advantage of at least tenfold. Furthermore, 10\u00a0mg\u00a0kg\n                    <jats:sup>\u22121<\/jats:sup>\n                    of 73\u2010DY sustainably suppressed serum viral levels to undetectable levels for \u2248 2 weeks. Molecular analyses indicate that the improved efficacy exhibited by 73\u2010DY is attributable to the synergy between fragment antigen binding (Fab) and fragment crystallizable (Fc) engineering, which conferred sustained viral suppression and robust viral eradication, respectively. Long\u2010term immunotherapy with reverse chimeric 73\u2010DY facilitated the restoration of anti\u2010HBV immune responses. This study provides a foundation for the development of next\u2010generation antibody\u2010based CHB therapies.\n                  <\/jats:p>","DOI":"10.1002\/advs.202305316","type":"journal-article","created":{"date-parts":[[2024,2,11]],"date-time":"2024-02-11T21:28:50Z","timestamp":1707686930000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["A Dual\u2010domain Engineered Antibody for Efficient HBV Suppression and Immune Responses Restoration"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-8657-2776","authenticated-orcid":false,"given":"Yichao","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Vaccines for Infectious Diseases Xiang An Biomedicine Laboratory School of Public Health School of Life Sciences Xiamen University  Xiamen 361102 P.R. 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