Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD

Sun, Hui1,2,3; Deng, Tingting1,2,3; Zhang, Yali1,2,3,4; Lin, Yanling1,2,3; Jiang, Yanan1,2,3; Jiang, Yichao1,2,3; Huang, Yang1,2,3; Song, Shuo5,6; Cui, Lingyan1,2,3; Li, Tingting1,2,3,4; Xiong, Hualong1,2,3,4; Lan, Miaolin1,2,3; Liu, Liqin1,2,3; Li, Yu1,2,3; Fang, Qianjiao1,2,3; Yu, Kunyu1,2,3; Jiang, Wenling1,2,3; Zhou, Lizhi1,2,3,4; Que, Yuqiong1,2,3,4; Zhang, Tianying1,2,3,4; Yuan, Quan1,2,3,4; Cheng, Tong1,2,3,4; Zhang, Zheng5,6; Yu, Hai1,2,3,4; Zhang, Jun1,2,3,4; Luo, Wenxin1,2,3,4; Li, Shaowei1,2,3,4; Zheng, Qingbing1,2,3,4; Gu, Ying1,2,3,4; Xia, Ningshao1,2,3,4,7

2023-07-01

10.1093/procel/pwad040

PROTEIN & CELL   Impact Factor & Quartile

1674-800X

1674-8018

Continual evolution of the severe acute respiratory syndrome coronavirus (SARS-CoV-2) virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs (bnAbs) and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two angiotensin-converting enzyme 2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-electron microscopy reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the receptor-binding domain to avoid steric clashing. Bispecific antibodies based on these two nAbs tremendously extend the neutralizing breadth and restore neutralization against recent variants including currently dominant XBB.1.5. Together, these findings expand our understanding of the potential strategies for the neutralization of SARS-CoV-2 variants toward the design of broad-acting antibody therapeutics and vaccines.

SARS-CoV-2 broad neutralizing antibody rearrangement synergistic neutralization

SCI

English

Others

Cell Biology

Cell Biology

WOS:001043062500001

OXFORD UNIV PRESS

Web of Science

1.Xiamen Univ, Sch Publ Hlth, Sch Life Sci, State Key Lab Mol Vaccinol & Mol Diagnost, Xiamen 361102, Peoples R China
2.Xiamen Univ, Natl Inst Diagnost & Vaccine Dev Infect Dis, Sch Publ Hlth, Sch Life Sci, Xiamen 361102, Peoples R China
3.Xiamen Univ, Sch Publ Hlth, Sch Life Sci, State Key Lab Vaccines Infect Dis, Xiamen 361102, Peoples R China
4.Xiang An Biomed Lab, Xiamen 361102, Peoples R China
5.Southern Univ Sci & Technol, Shenzhen Peoples Hosp 3, Inst Hepatol, Natl Clin Res Ctr Infect Dis,Sch Med, Shenzhen 518112, Peoples R China
6.Southern Univ Sci & Technol, Affiliated Hosp 2, Sch Med, Shenzhen 518112, Peoples R China
7.Chinese Acad Med Sci, Res Unit Frontier Technol Struct Vaccinol, Xiamen 361102, Peoples R China

Sun, Hui,Deng, Tingting,Zhang, Yali,et al. Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD[J]. PROTEIN & CELL,2023.

Sun, Hui.,Deng, Tingting.,Zhang, Yali.,Lin, Yanling.,Jiang, Yanan.,...&Xia, Ningshao.(2023).Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD.PROTEIN & CELL.

Sun, Hui,et al."Two antibodies show broad, synergistic neutralization against SARS-CoV-2 variants by inducing conformational change within the RBD".PROTEIN & CELL (2023).