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

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. © 2023. The Author(s).

Citation

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, Zihe Rao. Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection. Nature communications. 2023 Jun 15;14(1):3537

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PMID: 37322000

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