Biparatopic antibody BA7208/7125 effectively neutralizes SARS-CoV-2 variants including Omicron BA.1-BA.5
-
Published:2023-01-07
Issue:1
Volume:9
Page:
-
ISSN:2056-5968
-
Container-title:Cell Discovery
-
language:en
-
Short-container-title:Cell Discov
Author:
Wang YanqunORCID, Yan An, Song Deyong, Dong Chuangchuang, Rao Muding, Gao Yuanzhu, Qi Ruxi, Ma Xiaomin, Wang Qiaoping, Xu Hongguang, Liu Hong, Han Jing, Duan Maoqin, Liu Shuo, Yu Xiaoping, Zong Mengqi, Feng Jianxia, Jiao Jie, Zhang Huimin, Li Min, Yu Beibei, Wang Yanxia, Meng Fanhao, Ni Xiaodan, Li Ying, Shen Zhenduo, Sun Baiping, Shao Xin, Zhao Haifeng, Zhao Yanyan, Li Rui, Zhang Yanan, Du Guangying, Lu Jun, You Chunna, Jiang Hua, Zhang Lu, Wang Lan, Dou Changlin, Liu ZhengORCID, Zhao JincunORCID
Abstract
AbstractSARS-CoV-2 Omicron subvariants have demonstrated extensive evasion from monoclonal antibodies (mAbs) developed for clinical use, which raises an urgent need to develop new broad-spectrum mAbs. Here, we report the isolation and analysis of two anti-RBD neutralizing antibodies BA7208 and BA7125 from mice engineered to produce human antibodies. While BA7125 showed broadly neutralizing activity against all variants except the Omicron sublineages, BA7208 was potently neutralizing against all tested SARS-CoV-2 variants (including Omicron BA.1–BA.5) except Mu. By combining BA7208 and BA7125 through the knobs-into-holes technology, we generated a biparatopic antibody BA7208/7125 that was able to neutralize all tested circulating SARS-CoV-2 variants. Cryo-electron microscopy structure of these broad-spectrum antibodies in complex with trimeric Delta and Omicron spike indicated that the contact residues are highly conserved and had minimal interactions with mutational residues in RBD of current variants. In addition, we showed that administration of BA7208/7125 via the intraperitoneal, intranasal, or aerosol inhalation route showed potent therapeutic efficacy against Omicron BA.1 and BA.2 in hACE2-transgenic and wild-type mice and, separately, effective prophylaxis. BA7208/7125 thus has the potential to be an effective candidate as an intervention against COVID-19.
Funder
National Natural Science Foundation of China
Publisher
Springer Science and Business Media LLC
Subject
Cell Biology,Genetics,Molecular Biology,Biochemistry
Reference54 articles.
1. Jones, B. E. et al. The neutralizing antibody, LY-CoV555, protects against SARS-CoV-2 infection in nonhuman primates. Sci. Transl. Med. 13, eabf1906 (2021). 2. Shi, R. et al. A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2. Nature 584, 120–124 (2020). 3. Hansen, J. et al. Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail. Science 369, 1010–1014 (2020). 4. Zost, S. J. et al. Potently neutralizing and protective human antibodies against SARS-CoV-2. Nature 584, 443–449 (2020). 5. Pinto, D. et al. Cross-neutralization of SARS-CoV-2 by a human monoclonal SARS-CoV antibody. Nature 583, 290–295 (2020).
Cited by
10 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|