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Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies

Author

Listed:
  • Allison J. Greaney

    (Fred Hutchinson Cancer Research Center
    University of Washington)

  • Tyler N. Starr

    (Fred Hutchinson Cancer Research Center
    Howard Hughes Medical Institute)

  • Christopher O. Barnes

    (California Institute of Technology)

  • Yiska Weisblum

    (The Rockefeller University)

  • Fabian Schmidt

    (The Rockefeller University)

  • Marina Caskey

    (The Rockefeller University)

  • Christian Gaebler

    (The Rockefeller University)

  • Alice Cho

    (The Rockefeller University)

  • Marianna Agudelo

    (The Rockefeller University)

  • Shlomo Finkin

    (The Rockefeller University)

  • Zijun Wang

    (The Rockefeller University)

  • Daniel Poston

    (The Rockefeller University)

  • Frauke Muecksch

    (The Rockefeller University)

  • Theodora Hatziioannou

    (The Rockefeller University)

  • Paul D. Bieniasz

    (Howard Hughes Medical Institute
    The Rockefeller University)

  • Davide F. Robbiani

    (The Rockefeller University
    Universita della Svizzera italiana (USI))

  • Michel C. Nussenzweig

    (Howard Hughes Medical Institute
    The Rockefeller University)

  • Pamela J. Bjorkman

    (California Institute of Technology)

  • Jesse D. Bloom

    (Fred Hutchinson Cancer Research Center
    Howard Hughes Medical Institute)

Abstract

Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions of these different antibody classes to the polyclonal response remains unclear. Here we use a yeast-display system to map all mutations to the viral spike receptor-binding domain (RBD) that escape binding by representatives of three potently neutralizing classes of anti-RBD antibodies with high-resolution structures. We compare the antibody-escape maps to similar maps for convalescent polyclonal plasmas, including plasmas from individuals from whom some of the antibodies were isolated. While the binding of polyclonal plasma antibodies are affected by mutations across multiple RBD epitopes, the plasma-escape maps most resemble those of a single class of antibodies that target an epitope on the RBD that includes site E484. Therefore, although the human immune system can produce antibodies that target diverse RBD epitopes, in practice the polyclonal response to infection is skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.

Suggested Citation

  • Allison J. Greaney & Tyler N. Starr & Christopher O. Barnes & Yiska Weisblum & Fabian Schmidt & Marina Caskey & Christian Gaebler & Alice Cho & Marianna Agudelo & Shlomo Finkin & Zijun Wang & Daniel P, 2021. "Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
  • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24435-8
    DOI: 10.1038/s41467-021-24435-8
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    Cited by:

    1. Beatriz Álvarez-Rodríguez & Javier Buceta & Ron Geller, 2023. "Comprehensive profiling of neutralizing polyclonal sera targeting coxsackievirus B3," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. 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.
    3. Sheri Harari & Danielle Miller & Shay Fleishon & David Burstein & Adi Stern, 2024. "Using big sequencing data to identify chronic SARS-Coronavirus-2 infections," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    4. Leire Campos-Mata & Benjamin Trinité & Andrea Modrego & Sonia Tejedor Vaquero & Edwards Pradenas & Anna Pons-Grífols & Natalia Rodrigo Melero & Diego Carlero & Silvia Marfil & César Santiago & Dàlia R, 2024. "A monoclonal antibody targeting a large surface of the receptor binding motif shows pan-neutralizing SARS-CoV-2 activity," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    5. Yubin Liu & Ziyi Wang & Xinyu Zhuang & Shengnan Zhang & Zhicheng Chen & Yan Zou & Jie Sheng & Tianpeng Li & Wanbo Tai & Jinfang Yu & Yanqun Wang & Zhaoyong Zhang & Yunfeng Chen & Liangqin Tong & Xi Yu, 2023. "Inactivated vaccine-elicited potent antibodies can broadly neutralize SARS-CoV-2 circulating variants," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    6. Farina Karim & Catherine Riou & Mallory Bernstein & Zesuliwe Jule & Gila Lustig & Strauss Graan & Roanne S. Keeton & Janine-Lee Upton & Yashica Ganga & Khadija Khan & Kajal Reedoy & Matilda Mazibuko &, 2024. "Clearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    7. Emanuele Andreano & Ida Paciello & Silvia Marchese & Lorena Donnici & Giulio Pierleoni & Giulia Piccini & Noemi Manganaro & Elisa Pantano & Valentina Abbiento & Piero Pileri & Linda Benincasa & Ginevr, 2022. "Anatomy of Omicron BA.1 and BA.2 neutralizing antibodies in COVID-19 mRNA vaccinees," Nature Communications, Nature, vol. 13(1), pages 1-8, December.
    8. Cathrine Scheepers & Josie Everatt & Daniel G. Amoako & Houriiyah Tegally & Constantinos Kurt Wibmer & Anele Mnguni & Arshad Ismail & Boitshoko Mahlangu & Bronwen E. Lambson & Darren P. Martin & Eduan, 2022. "Emergence and phenotypic characterization of the global SARS-CoV-2 C.1.2 lineage," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    9. Wenkai Han & Ningning Chen & Xinzhou Xu & Adil Sahil & Juexiao Zhou & Zhongxiao Li & Huawen Zhong & Elva Gao & Ruochi Zhang & Yu Wang & Shiwei Sun & Peter Pak-Hang Cheung & Xin Gao, 2023. "Predicting the antigenic evolution of SARS-COV-2 with deep learning," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    10. Chang Liu & Raksha Das & Aiste Dijokaite-Guraliuc & Daming Zhou & Alexander J. Mentzer & Piyada Supasa & Muneeswaran Selvaraj & Helen M. E. Duyvesteyn & Thomas G. Ritter & Nigel Temperton & Paul Klene, 2024. "Emerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection," Nature Communications, Nature, vol. 15(1), pages 1-10, December.
    11. Chengzi I. Kaku & Tyler N. Starr & Panpan Zhou & Haley L. Dugan & Paul Khalifé & Ge Song & Elizabeth R. Champney & Daniel W. Mielcarz & James C. Geoghegan & Dennis R. Burton & Raiees Andrabi & Jesse D, 2023. "Evolution of antibody immunity following Omicron BA.1 breakthrough infection," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    12. Alief Moulana & Thomas Dupic & Angela M. Phillips & Jeffrey Chang & Serafina Nieves & Anne A. Roffler & Allison J. Greaney & Tyler N. Starr & Jesse D. Bloom & Michael M. Desai, 2022. "Compensatory epistasis maintains ACE2 affinity in SARS-CoV-2 Omicron BA.1," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    13. Ana S. Gonzalez-Reiche & Hala Alshammary & Sarah Schaefer & Gopi Patel & Jose Polanco & Juan Manuel Carreño & Angela A. Amoako & Aria Rooker & Christian Cognigni & Daniel Floda & Adriana Guchte & Zain, 2023. "Sequential intrahost evolution and onward transmission of SARS-CoV-2 variants," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

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