A glycoengineered therapeutic anti-HBV antibody that allows increased HBsAg immunoclearance improves HBV suppression in vivo

You, Min1; Chen, Fentian1; Yu, Chao1; Chen, Yuanzhi1; Wang, Yue1; Liu, Xue1; Guo, Xueran1; Zhou, Bing1,2; Wang, Xin1,2; Zhang, Boya1; Fang, Mujin1,3; Zhang, Tianying1,3; Yue, Ping4; Wang, Yingbin1,3; Yuan, Quan1,3; Luo, Wenxin1,3

2023-12-27

10.3389/fphar.2023.1213726

FRONTIERS IN PHARMACOLOGY   影响因子和分区

1663-9812

Introduction: The effective and persistent suppression of hepatitis B surface antigen (HBsAg) in patients with chronic HBV infection (CHB) is considered to be a promising approach to achieve a functional cure of hepatitis B. In our previous study, we found that the antibody E6F6 can clear HBsAg through Fc gamma R-mediated phagocytosis, and its humanized form (huE6F6 antibody) is expected to be a new tool for the treatment of CHB. Previous studies have shown that the glycosylation of Fc segments affects the binding of antibodies to Fc gamma R and thus affects the biological activity of antibodies in vivo.Methods: To further improve the therapeutic potential of huE6F6, in this study, we defucosylated huE6F6 (huE6F6-fuc-), preliminarily explored the developability of this molecule, and studied the therapeutic potential of this molecule and its underlying mechanism in vitro and in vivo models.Results: huE6F6-fuc- has desirable physicochemical properties. Compared with huE6F6-wt, huE6F6-fuc- administration resulted in a stronger viral clearance in vivo. Meanwhile, huE6F6-fuc- keep a similar neutralization activity and binding activity to huE6F6-wt in vitro. Immunological analyses suggested that huE6F6-fuc- exhibited enhanced binding to hCD32b and hCD16b, which mainly contributed to its enhanced therapeutic activity in vivo.Conclusions: In summary, the huE6F6-fuc- molecule that was developed in this study, which has desirable developability, can clear HBsAg more efficiently in vivo, providing a promising treatment for CHB patients. Our study provides new guidance for antibody engineering in other disease fields.

HBsAg chronic hepatitis B infection therapeutic antibody phagocytosis neutralization defucosylation

SCI

英语

其他

National Natural Science Foundation of China["31900675","U1905205","32070940","82202500","32170943"] ; Youth Innovation Fund of Xiamen[3502Z20206060] ; China Postdoctoral Science Foundation[2021M700115] ; Guizhou Provincial Science and Technology Project[ZK 2022-397]

Pharmacology & Pharmacy

Pharmacology & Pharmacy

WOS:001139364000001

FRONTIERS MEDIA SA

Web of Science

1.Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Sch Life Sci, Sch Publ Hlth,State Key Lab Mol Vaccinol & Mol Dia, Xiamen, Peoples R China
2.South Univ Sci & Technol, Affiliated Hosp 2, Shenzhen, Peoples R China
3.Xiang An Biomed Lab, Xiamen, Peoples R China
4.Guizhou Med Univ, Immune Cells & Antibody Engn Res Ctr Univ Guizhou, Sch Biol & Engn, Sch Hlth Med Modern Ind, Guiyang, Peoples R China

You, Min,Chen, Fentian,Yu, Chao,et al. A glycoengineered therapeutic anti-HBV antibody that allows increased HBsAg immunoclearance improves HBV suppression in vivo[J]. FRONTIERS IN PHARMACOLOGY,2023,14.

You, Min.,Chen, Fentian.,Yu, Chao.,Chen, Yuanzhi.,Wang, Yue.,...&Luo, Wenxin.(2023).A glycoengineered therapeutic anti-HBV antibody that allows increased HBsAg immunoclearance improves HBV suppression in vivo.FRONTIERS IN PHARMACOLOGY,14.

You, Min,et al."A glycoengineered therapeutic anti-HBV antibody that allows increased HBsAg immunoclearance improves HBV suppression in vivo".FRONTIERS IN PHARMACOLOGY 14(2023).