Potent neutralization of SARS-CoV-2 variants of concern by an antibody with an uncommon genetic signature and structural mode of spike recognition

Kevin J. Kramer, Nicole V. Johnson, Andrea R. Shiakolas, Naveenchandra Suryadevara, Sivakumar Periasamy, Nagarajan Raju, Jazmean K. Williams, Daniel Wrapp, Seth J. Zost, Lauren M. Walker, Steven C. Wall, Clinton M. Holt, Ching Lin Hsieh, Rachel E. Sutton, Ariana Paulo, Rachel S. Nargi, Edgar Davidson, Benjamin J. Doranz, James E. Crowe, Alexander BukreyevRobert H. Carnahan, Jason S. McLellan, Ivelin S. Georgiev

    Research output: Contribution to journalArticlepeer-review

    9 Scopus citations

    Abstract

    The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineages that are more transmissible and resistant to currently approved antibody therapies poses a considerable challenge to the clinical treatment of coronavirus disease (COVID-19). Therefore, the need for ongoing discovery efforts to identify broadly reactive monoclonal antibodies to SARS-CoV-2 is of utmost importance. Here, we report a panel of SARS-CoV-2 antibodies isolated using the linking B cell receptor to antigen specificity through sequencing (LIBRA-seq) technology from an individual who recovered from COVID-19. Of these antibodies, 54042-4 shows potent neutralization against authentic SARS-CoV-2 viruses, including variants of concern (VOCs). A cryoelectron microscopy (cryo-EM) structure of 54042-4 in complex with the SARS-CoV-2 spike reveals an epitope composed of residues that are highly conserved in currently circulating SARS-CoV-2 lineages. Further, 54042-4 possesses uncommon genetic and structural characteristics that distinguish it from other potently neutralizing SARS-CoV-2 antibodies. Together, these findings provide motivation for the development of 54042-4 as a lead candidate to counteract current and future SARS-CoV-2 VOCs.

    Original languageEnglish (US)
    Article number109784
    JournalCell Reports
    Volume37
    Issue number1
    DOIs
    StatePublished - Oct 5 2021

    Keywords

    • COVID-19
    • Delta variant
    • LIBRA-seq
    • SARS-CoV-2
    • antibody discovery
    • cryo-EM
    • monoclonal antibodies biology

    ASJC Scopus subject areas

    • Biochemistry, Genetics and Molecular Biology(all)

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