Cell Reports (Oct 2021)
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, Jr.,
- Alexander Bukreyev,
- Robert H. Carnahan,
- Jason S. McLellan,
- Ivelin S. Georgiev
Affiliations
- Kevin J. Kramer
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Nicole V. Johnson
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
- Andrea R. Shiakolas
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Naveenchandra Suryadevara
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Sivakumar Periasamy
- Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
- Nagarajan Raju
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Jazmean K. Williams
- Integral Molecular, Philadelphia, PA 19104, USA
- Daniel Wrapp
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
- Seth J. Zost
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Lauren M. Walker
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Steven C. Wall
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Clinton M. Holt
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Ching-Lin Hsieh
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
- Rachel E. Sutton
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Ariana Paulo
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Rachel S. Nargi
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Edgar Davidson
- Integral Molecular, Philadelphia, PA 19104, USA
- Benjamin J. Doranz
- Integral Molecular, Philadelphia, PA 19104, USA
- James E. Crowe, Jr.
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Alexander Bukreyev
- Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA; Galveston National Laboratory, University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA
- Robert H. Carnahan
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Jason S. McLellan
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA; Corresponding author
- Ivelin S. Georgiev
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Vanderbilt Institute for Infection, Immunology, and Inflammation, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Department of Electrical Engineering and Computer Science, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Center for Structural Biology, Vanderbilt University, Nashville, TN 37232, USA; Program in Computational Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA; Corresponding author
- Journal volume & issue
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Vol. 37,
no. 1
p. 109784
Abstract
Summary: 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.
