Therapeutic Potential of the Novel Monoclonal Antibody 7-4G against HBsAg in a Mouse Model of Chronic Hepatitis B Virus Infection

Abuduwaili, M.; Makokha, G. N.; Naderi, M.; Sakai, H.; Yamamoto, A.; Sakaguchi, T.; Matsumoto, T.; Shirouzu, M.; Seishi, K.; Kubo, Y.; Matsushita, M.; Inoue, Y.; Shankhajit, D.; Hijikata, M.; Chayama, K.

doi:10.64898/2026.07.24.740663

bioRxiv · 10.64898/2026.07.24.740663

Therapeutic Potential of the Novel Monoclonal Antibody 7-4G against HBsAg in a Mouse Model of Chronic Hepatitis B Virus Infection

Abuduwaili, M.·Makokha, G. N.·Naderi, M.·Sakai, H.·Yamamoto, A.·Sakaguchi, T.·Matsumoto, T.·Shirouzu, M.·Seishi, K.·Kubo, Y.·Matsushita, M.·Inoue, Y.·Shankhajit, D.·Hijikata, M.·Chayama, K.

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Abstract

Chronic hepatitis B virus (HBV) infection remains a major global health challenge because current antiviral therapies rarely achieve complete viral clearance. We evaluated the antiviral activity of a newly developed monoclonal antibody, 7-4G mAb, directed against the hepatitis B surface antigen (HBsAg). The antibody showed specific binding to the p27 component of HBsAg and efficiently removed HBV-related particles from patient serum in vitro. Significant HBV neutralizing activity of 7-4G mAb was observed in primary human hepatocytes and in humanized mouse models. In persistently HBV-infected PXB mice, a single administration of 7-4G mAb, either alone or in combination with another monoclonal antibody, reduced serum HBsAg levels and HBV DNA levels by two orders magnitude for two weeks after the treatment. In half of the treated mice, suppression of both viral markers was maintained through the study period, whereas rebound occurred within three to four weeks in the remaining animals. In addition, 7-4G mAb enhanced the HBV DNA-lowering effect of entecavir, a known anti-HBV drug. These findings support the further development of 7-4G mAb as part of an innovative HBV treatment strategy, addressing limitations of existing therapies and advancing toward a more effective HBV management solution.

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Abuduwaili, M., Makokha, G. N., Naderi, M., Sakai, H., Yamamoto, A., Sakaguchi, T., Matsumoto, T., Shirouzu, M., Seishi, K., Kubo, Y., Matsushita, M., Inoue, Y., Shankhajit, D., Hijikata, M., Chayama, K.. 2026-07-26. Therapeutic Potential of the Novel Monoclonal Antibody 7-4G against HBsAg in a Mouse Model of Chronic Hepatitis B Virus Infection. https://doi.org/10.64898/2026.07.24.740663

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