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

Author

Listed:
  • Yu Guo

    (Nankai University
    Chinese Academy of Medical Sciences & Peking Union Medical College
    Guangzhou Laboratory
    China National Biotech Group)

  • Guangshun Zhang

    (Nankai University
    Guangzhou Laboratory
    Nankai University
    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
    Nankai University)

  • Jingxi Liang

    (Nankai University
    ShanghaiTech University)

  • Jielin Tang

    (Guangzhou Laboratory)

  • Yuxin Gao

    (Nankai University
    Nankai University
    Nankai University)

  • Hang Shang

    (Nankai University
    Nankai University
    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
    Chinese Academy of Medical Sciences & Peking Union Medical College)

  • 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
    Nankai University)

  • Song Zhang

    (Nankai University
    Nankai University)

  • Zhiyong Lou

    (Guangzhou Laboratory)

  • Yan Gao

    (ShanghaiTech University)

  • Zidan Song

    (Nankai University
    Guangzhou Laboratory
    Nankai University
    Nankai University)

  • Wenming Wang

    (Nankai University
    Nankai University
    Nankai University)

  • Zixian Sun

    (Guangzhou Laboratory)

  • Xiaoming Yang

    (China National Biotech Group
    Nankai University)

  • 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
    Guangzhou Laboratory
    Nankai University
    ShanghaiTech University)

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.

Suggested 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 G, 2023. "Discovery and characterization of potent pan-variant SARS-CoV-2 neutralizing antibodies from individuals with Omicron breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39267-x
    DOI: 10.1038/s41467-023-39267-x
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