IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39267-x.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39267-x
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-39267-x?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Sandile Cele & Laurelle Jackson & David S. Khoury & Khadija Khan & Thandeka Moyo-Gwete & Houriiyah Tegally & James Emmanuel San & Deborah Cromer & Cathrine Scheepers & Daniel G. Amoako & Farina Karim , 2022. "Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization," Nature, Nature, vol. 602(7898), pages 654-656, February.
    2. Seth J. Zost & Pavlo Gilchuk & James Brett Case & Elad Binshtein & Rita E. Chen & Joseph P. Nkolola & Alexandra Schäfer & Joseph X. Reidy & Andrew Trivette & Rachel S. Nargi & Rachel E. Sutton & Navee, 2020. "Potently neutralizing and protective human antibodies against SARS-CoV-2," Nature, Nature, vol. 584(7821), pages 443-449, August.
    3. Rui Shi & Chao Shan & Xiaomin Duan & Zhihai Chen & Peipei Liu & Jinwen Song & Tao Song & Xiaoshan Bi & Chao Han & Lianao Wu & Ge Gao & Xue Hu & Yanan Zhang & Zhou Tong & Weijin Huang & William Jun Liu, 2020. "A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2," Nature, Nature, vol. 584(7819), pages 120-124, August.
    4. Khadija Khan & Farina Karim & Yashica Ganga & Mallory Bernstein & Zesuliwe Jule & Kajal Reedoy & Sandile Cele & Gila Lustig & Daniel Amoako & Nicole Wolter & Natasha Samsunder & Aida Sivro & James Emm, 2022. "Author Correction: Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection," Nature Communications, Nature, vol. 13(1), pages 1-1, December.
    5. Mikhail Shugay & Dmitriy V Bagaev & Maria A Turchaninova & Dmitriy A Bolotin & Olga V Britanova & Ekaterina V Putintseva & Mikhail V Pogorelyy & Vadim I Nazarov & Ivan V Zvyagin & Vitalina I Kirgizova, 2015. "VDJtools: Unifying Post-analysis of T Cell Receptor Repertoires," PLOS Computational Biology, Public Library of Science, vol. 11(11), pages 1-16, November.
    6. Heidi Ledford, 2021. "Six months of COVID vaccines: what 1.7 billion doses have taught scientists," Nature, Nature, vol. 594(7862), pages 164-167, June.
    7. Khadija Khan & Farina Karim & Yashica Ganga & Mallory Bernstein & Zesuliwe Jule & Kajal Reedoy & Sandile Cele & Gila Lustig & Daniel Amoako & Nicole Wolter & Natasha Samsunder & Aida Sivro & James Emm, 2022. "Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    8. Qin Hong & Wenyu Han & Jiawei Li & Shiqi Xu & Yifan Wang & Cong Xu & Zuyang Li & Yanxing Wang & Chao Zhang & Zhong Huang & Yao Cong, 2022. "Molecular basis of receptor binding and antibody neutralization of Omicron," Nature, Nature, vol. 604(7906), pages 546-552, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Khadija Khan & Gila Lustig & Cornelius Römer & Kajal Reedoy & Zesuliwe Jule & Farina Karim & Yashica Ganga & Mallory Bernstein & Zainab Baig & Laurelle Jackson & Boitshoko Mahlangu & Anele Mnguni & Ay, 2023. "Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    2. Felix Dewald & Martin Pirkl & Martha Paluschinski & Joachim Kühn & Carina Elsner & Bianca Schulte & Jacqueline Knüfer & Elvin Ahmadov & Maike Schlotz & Göksu Oral & Michael Bernhard & Mark Michael & M, 2023. "Impaired humoral immunity to BQ.1.1 in convalescent and vaccinated patients," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    3. Zhennan Zhao & Yufeng Xie & Bin Bai & Chunliang Luo & Jingya Zhou & Weiwei Li & Yumin Meng & Linjie Li & Dedong Li & Xiaomei Li & Xiaoxiong Li & Xiaoyun Wang & Junqing Sun & Zepeng Xu & Yeping Sun & W, 2023. "Structural basis for receptor binding and broader interspecies receptor recognition of currently circulating Omicron sub-variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Yanqun Wang & An Yan & Deyong Song & Maoqin Duan & Chuangchuang Dong & Jiantao Chen & Zihe Jiang & Yuanzhu Gao & Muding Rao & Jianxia Feng & Zhaoyong Zhang & Ruxi Qi & Xiaomin Ma & Hong Liu & Beibei Y, 2024. "Identification of a highly conserved neutralizing epitope within the RBD region of diverse SARS-CoV-2 variants," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    5. Yingdan Wang & Aihua Hao & Ping Ji & Yunping Ma & Zhaoyong Zhang & Jiali Chen & Qiyu Mao & Xinyi Xiong & Palizhati Rehati & Yajie Wang & Yanqun Wang & Yumei Wen & Lu Lu & Zhenguo Chen & Jincun Zhao & , 2024. "A bispecific antibody exhibits broad neutralization against SARS-CoV-2 Omicron variants XBB.1.16, BQ.1.1 and sarbecoviruses," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    6. Peter J. Halfmann & Kathryn Loeffler & Augustine Duffy & Makoto Kuroda & Jie E. Yang & Elizabeth R. Wright & Yoshihiro Kawaoka & Ravi S. Kane, 2024. "Broad protection against clade 1 sarbecoviruses after a single immunization with cocktail spike-protein-nanoparticle vaccine," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    7. Tingting Li & Xiaojian Han & Chenjian Gu & Hangtian Guo & Huajun Zhang & Yingming Wang & Chao Hu & Kai Wang & Fengjiang Liu & Feiyang Luo & Yanan Zhang & Jie Hu & Wang Wang & Shenglong Li & Yanan Hao , 2021. "Potent SARS-CoV-2 neutralizing antibodies with protective efficacy against newly emerged mutational variants," Nature Communications, Nature, vol. 12(1), pages 1-11, December.
    8. Emanuele Andreano & Ida Paciello & Giulio Pierleoni & Giuseppe Maccari & Giada Antonelli & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevra Giglioli & Giulia Piccini & Concetta De Santi &, 2023. "mRNA vaccines and hybrid immunity use different B cell germlines against Omicron BA.4 and BA.5," Nature Communications, Nature, vol. 14(1), pages 1-9, December.
    9. Yifan Wang & Caixuan Liu & Chao Zhang & Yanxing Wang & Qin Hong & Shiqi Xu & Zuyang Li & Yong Yang & Zhong Huang & Yao Cong, 2022. "Structural basis for SARS-CoV-2 Delta variant recognition of ACE2 receptor and broadly neutralizing antibodies," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    10. Magen E. Francis & Ethan B. Jansen & Anthony Yourkowski & Alaa Selim & Cynthia L. Swan & Brian K. MacPhee & Brittany Thivierge & Rachelle Buchanan & Kerry J. Lavender & Joseph Darbellay & Matthew B. R, 2023. "Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    11. Andrew C. Hunt & Bastian Vögeli & Ahmed O. Hassan & Laura Guerrero & Weston Kightlinger & Danielle J. Yoesep & Antje Krüger & Madison DeWinter & Michael S. Diamond & Ashty S. Karim & Michael C. Jewett, 2023. "A rapid cell-free expression and screening platform for antibody discovery," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    12. Bo Zhang & Youyi Fong & Jonathan Fintzi & Eric Chu & Holly E. Janes & Avi Kenny & Marco Carone & David Benkeser & Lars W. P. Laan & Weiping Deng & Honghong Zhou & Xiaowei Wang & Yiwen Lu & Chenchen Yu, 2024. "Omicron COVID-19 immune correlates analysis of a third dose of mRNA-1273 in the COVE trial," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    13. Pauline Maisonnasse & Yoann Aldon & Aurélien Marc & Romain Marlin & Nathalie Dereuddre-Bosquet & Natalia A. Kuzmina & Alec W. Freyn & Jonne L. Snitselaar & Antonio Gonçalves & Tom G. Caniels & Judith , 2021. "COVA1-18 neutralizing antibody protects against SARS-CoV-2 in three preclinical models," Nature Communications, Nature, vol. 12(1), pages 1-10, December.
    14. Daming Zhou & Piyada Supasa & Chang Liu & Aiste Dijokaite-Guraliuc & Helen M. E. Duyvesteyn & Muneeswaran Selvaraj & Alexander J. Mentzer & Raksha Das & Wanwisa Dejnirattisai & Nigel Temperton & Paul , 2024. "The SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    15. Mike B. Barnkob & Yale S. Michaels & Violaine André & Philip S. Macklin & Uzi Gileadi & Salvatore Valvo & Margarida Rei & Corinna Kulicke & Ji-Li Chen & Vitul Jain & Victoria K. Woodcock & Huw Colin-Y, 2024. "Semaphorin 3A causes immune suppression by inducing cytoskeletal paralysis in tumour-specific CD8+ T cells," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    16. Taha Y. Taha & Irene P. Chen & Jennifer M. Hayashi & Takako Tabata & Keith Walcott & Gabriella R. Kimmerly & Abdullah M. Syed & Alison Ciling & Rahul K. Suryawanshi & Hannah S. Martin & Bryan H. Bach , 2023. "Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    17. Song Li & Wenbin Yu & Fei Xie & Haitao Luo & Zhimin Liu & Weiwei Lv & Duanbo Shi & Dexin Yu & Peng Gao & Cheng Chen & Meng Wei & Wenhao Zhou & Jiaqian Wang & Zhikun Zhao & Xin Dai & Qian Xu & Xue Zhan, 2023. "Neoadjuvant therapy with immune checkpoint blockade, antiangiogenesis, and chemotherapy for locally advanced gastric cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    18. Guoli Shi & Tiansheng Li & Kin Kui Lai & Reed F. Johnson & Jonathan W. Yewdell & Alex A. Compton, 2024. "Omicron Spike confers enhanced infectivity and interferon resistance to SARS-CoV-2 in human nasal tissue," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    19. Haisheng Yu & Banghui Liu & Yudi Zhang & Xijie Gao & Qian Wang & Haitao Xiang & Xiaofang Peng & Caixia Xie & Yaping Wang & Peiyu Hu & Jingrong Shi & Quan Shi & Pingqian Zheng & Chengqian Feng & Guofan, 2023. "Somatically hypermutated antibodies isolated from SARS-CoV-2 Delta infected patients cross-neutralize heterologous variants," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. Kevin J. Kramer & Erin M. Wilfong & Kelsey Voss & Sierra M. Barone & Andrea R. Shiakolas & Nagarajan Raju & Caroline E. Roe & Naveenchandra Suryadevara & Lauren M. Walker & Steven C. Wall & Ariana Pau, 2022. "Single-cell profiling of the antigen-specific response to BNT162b2 SARS-CoV-2 RNA vaccine," Nature Communications, Nature, vol. 13(1), pages 1-20, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39267-x. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.