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Cell
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Deep mutational scanning identifies SARS-CoV-2 Nucleocapsid escape mutations of currently available rapid antigen tests

  • Filipp Frank
    Correspondence
    Corresponding author
    Affiliations
    Emory University School of Medicine, Department of Biochemistry, Emory University, Atlanta, GA 30322, USA
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  • Meredith M. Keen
    Affiliations
    Emory University School of Medicine, Department of Biochemistry, Emory University, Atlanta, GA 30322, USA
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  • Anuradha Rao
    Affiliations
    The Atlanta Center for Microsystems-Engineered Point-of-Care Technologies, Atlanta, GA 30322, USA

    Emory University School of Medicine, Department of Pediatrics, Atlanta, GA 30322, USA

    Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta and Emory University, Atlanta, GA 30322, USA
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  • Leda Bassit
    Affiliations
    The Atlanta Center for Microsystems-Engineered Point-of-Care Technologies, Atlanta, GA 30322, USA

    Emory University School of Medicine, Department of Pediatrics, Atlanta, GA 30322, USA

    Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta and Emory University, Atlanta, GA 30322, USA
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  • Xu Liu
    Affiliations
    Emory University School of Medicine, Department of Biochemistry, Emory University, Atlanta, GA 30322, USA
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  • Heather B. Bowers
    Affiliations
    The Atlanta Center for Microsystems-Engineered Point-of-Care Technologies, Atlanta, GA 30322, USA

    Emory University School of Medicine, Department of Pediatrics, Atlanta, GA 30322, USA

    Center for Childhood Infections and Vaccines of Children’s Healthcare of Atlanta and Emory University, Atlanta, GA 30322, USA
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  • Anamika B. Patel
    Affiliations
    Emory University School of Medicine, Department of Biochemistry, Emory University, Atlanta, GA 30322, USA
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  • Michael L. Cato
    Affiliations
    Emory University School of Medicine, Department of Biochemistry, Emory University, Atlanta, GA 30322, USA
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  • Julie A. Sullivan
    Affiliations
    The Atlanta Center for Microsystems-Engineered Point-of-Care Technologies, Atlanta, GA 30322, USA

    Emory University School of Medicine, Department of Pediatrics, Atlanta, GA 30322, USA
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  • Morgan Greenleaf
    Affiliations
    The Atlanta Center for Microsystems-Engineered Point-of-Care Technologies, Atlanta, GA 30322, USA

    Emory University School of Medicine, Department of Pediatrics, Atlanta, GA 30322, USA
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  • Anne Piantadosi
    Affiliations
    Emory University School of Medicine, Department of Pathology and Laboratory Medicine, Atlanta, GA 30322, USA

    Emory University School of Medicine, Department of Medicine, Division of Infectious Diseases, Atlanta, GA 30322, USA
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  • Wilbur A. Lam
    Affiliations
    The Atlanta Center for Microsystems-Engineered Point-of-Care Technologies, Atlanta, GA 30322, USA

    Emory University School of Medicine, Department of Pediatrics, Atlanta, GA 30322, USA

    Wallace H. Coulter Department of Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA 30332, USA

    Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, Atlanta, GA 30322, USA
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  • Author Footnotes
    10 Current address: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
    William H. Hudson
    Correspondence
    Corresponding author
    Footnotes
    10 Current address: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
    Affiliations
    Emory Vaccine Center and Emory University School of Medicine, Department of Microbiology and Immunology, Atlanta, GA 30322 USA
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  • Author Footnotes
    11 Lead contact
    Eric A. Ortlund
    Correspondence
    Corresponding author
    Footnotes
    11 Lead contact
    Affiliations
    Emory University School of Medicine, Department of Biochemistry, Emory University, Atlanta, GA 30322, USA
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  • Author Footnotes
    10 Current address: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
    11 Lead contact
Open AccessPublished:August 26, 2022DOI:https://doi.org/10.1016/j.cell.2022.08.010

      Highlights

      • A mammalian surface-display platform for SARS-CoV-2 Nucleocapsid protein
      • Measured the effects of all Nucleocapsid mutations on antibody recognition
      • Provide escape mutation profiles for 17 antibodies used in 11 diagnostic tests
      • Rapid antigen tests efficiently detect all current and previous SARS-CoV-2 variants

      Summary

      The effects of mutations in continuously emerging variants of SARS-CoV-2 are a major concern for the performance of rapid antigen tests. To evaluate the impact of mutations on 17 antibodies used in 11 commercially available antigen tests with emergency use authorization we measured antibody binding for all possible Nucleocapsid point mutations using a mammalian surface-display platform and deep mutational scanning. The results provide a complete map of the antibodies’ epitopes and their susceptibility to mutational escape. Our data predict no vulnerabilities for detection of mutations found in variants of concern. We confirm this using the commercial tests and sequence-confirmed COVID-19 patient samples. The antibody escape mutational profiles generated here serve as a valuable resource for predicting the performance of rapid antigen tests against past, current, as well as any possible future variants of SARS-CoV-2, establishing the direct clinical and public health utility of our system.

      Graphical abstract