Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection

Yu Guo (), Guangshun Zhang, Qi Yang (), Xiaowei Xie, Yang Lu, Xuelian Cheng, Hui Wang, Jingxi Liang, Jielin Tang, Yuxin Gao, Hang Shang, Jun Dai, Yongxia Shi, Jiaxi Zhou, Jun Zhou, Hangtian Guo, Haitao Yang, Jianwei Qi, Lijun Liu, Shihui Ma, Biao Zhang, Qianyu Huo, Yi Xie, Junping Wu, Fang Dong, Song Zhang, Zhiyong Lou, Yan Gao, Zidan Song, Wenming Wang, Zixian Sun, Xiaoming Yang (), Dongsheng Xiong (), Fengjiang Liu (), Xinwen Chen (), Ping Zhu (), Ximo Wang (), Tao Cheng () and Zihe Rao ()
Additional contact information
Yu Guo: Nankai University
Guangshun Zhang: Nankai University
Qi Yang: Guangzhou Laboratory
Xiaowei Xie: Chinese Academy of Medical Sciences & Peking Union Medical College
Yang Lu: Chinese Academy of Medical Sciences & Peking Union Medical College
Xuelian Cheng: Chinese Academy of Medical Sciences & Peking Union Medical College
Hui Wang: China National Biotech Group
Jingxi Liang: Nankai University
Jielin Tang: Guangzhou Laboratory
Yuxin Gao: Nankai University
Hang Shang: Nankai University
Jun Dai: Guangzhou Customs District Technology Center
Yongxia Shi: Guangzhou Customs District Technology Center
Jiaxi Zhou: Chinese Academy of Medical Sciences & Peking Union Medical College
Jun Zhou: Nankai University
Hangtian Guo: ShanghaiTech University
Haitao Yang: ShanghaiTech University
Jianwei Qi: Chinese Academy of Medical Sciences & Peking Union Medical College
Lijun Liu: Chinese Academy of Medical Sciences & Peking Union Medical College
Shihui Ma: Chinese Academy of Medical Sciences & Peking Union Medical College
Biao Zhang: Chinese Academy of Medical Sciences & Peking Union Medical College
Qianyu Huo: Chinese Academy of Medical Sciences & Peking Union Medical College
Yi Xie: Tianjin Haihe Hospital
Junping Wu: Tianjin Haihe Hospital
Fang Dong: Nankai University
Song Zhang: Nankai University
Zhiyong Lou: Guangzhou Laboratory
Yan Gao: ShanghaiTech University
Zidan Song: Nankai University
Wenming Wang: Nankai University
Zixian Sun: Guangzhou Laboratory
Xiaoming Yang: China National Biotech Group
Dongsheng Xiong: Chinese Academy of Medical Sciences & Peking Union Medical College
Fengjiang Liu: Guangzhou Laboratory
Xinwen Chen: Guangzhou Laboratory
Ping Zhu: Chinese Academy of Medical Sciences & Peking Union Medical College
Ximo Wang: Tianjin Haihe Hospital
Tao Cheng: Chinese Academy of Medical Sciences & Peking Union Medical College
Zihe Rao: Nankai University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract The SARS-CoV-2 Omicron variant evades most currently approved neutralizing antibodies (nAbs) and caused drastic decrease of plasma neutralizing activity elicited by vaccination or prior infection, urging the need for the development of pan-variant antivirals. Breakthrough infection induces a hybrid immunological response with potentially broad, potent and durable protection against variants, therefore, convalescent plasma from breakthrough infection may provide a broadened repertoire for identifying elite nAbs. We performed single-cell RNA sequencing (scRNA-seq) and BCR sequencing (scBCR-seq) of B cells from BA.1 breakthrough-infected patients who received 2 or 3 previous doses of inactivated vaccine. Elite nAbs, mainly derived from the IGHV2–5 and IGHV3-66/53 germlines, showed potent neutralizing activity across Wuhan-Hu-1, Delta, Omicron sublineages BA.1 and BA.2 at picomolar NT50 values. Cryo-EM analysis revealed diverse modes of spike recognition and guides the design of cocktail therapy. A single injection of paired antibodies cocktail provided potent protection in the K18-hACE2 transgenic female mouse model of SARS-CoV-2 infection.

Date: 2023
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DOI: 10.1038/s41467-023-39267-x

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