Cell Reports Medicine (Jun 2021)
Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions
- Andrea R. Shiakolas,
- Kevin J. Kramer,
- Daniel Wrapp,
- Simone I. Richardson,
- Alexandra Schäfer,
- Steven Wall,
- Nianshuang Wang,
- Katarzyna Janowska,
- Kelsey A. Pilewski,
- Rohit Venkat,
- Robert Parks,
- Nelia P. Manamela,
- Nagarajan Raju,
- Emilee Friedman Fechter,
- Clinton M. Holt,
- Naveenchandra Suryadevara,
- Rita E. Chen,
- David R. Martinez,
- Rachel S. Nargi,
- Rachel E. Sutton,
- Julie E. Ledgerwood,
- Barney S. Graham,
- Michael S. Diamond,
- Barton F. Haynes,
- Priyamvada Acharya,
- Robert H. Carnahan,
- James E. Crowe, Jr.,
- Ralph S. Baric,
- Lynn Morris,
- Jason S. McLellan,
- Ivelin S. Georgiev
Affiliations
- 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
- 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
- Daniel Wrapp
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
- Simone I. Richardson
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
- Alexandra Schäfer
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA
- Steven Wall
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Nianshuang Wang
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
- Katarzyna Janowska
- Division of Structural Biology, Duke University School of Medicine, Durham, NC 27710, USA
- Kelsey A. Pilewski
- 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
- Rohit Venkat
- 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
- Robert Parks
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Nelia P. Manamela
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
- Nagarajan Raju
- 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
- Emilee Friedman Fechter
- Vanderbilt Vaccine Center, 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
- Naveenchandra Suryadevara
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Rita E. Chen
- Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA
- David R. Martinez
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA
- Rachel S. Nargi
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Rachel E. Sutton
- Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA
- Julie E. Ledgerwood
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Barney S. Graham
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
- Michael S. Diamond
- Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA
- Barton F. Haynes
- Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA
- Priyamvada Acharya
- Division of Structural Biology, Duke University School of Medicine, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, 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
- 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
- Ralph S. Baric
- Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA
- Lynn Morris
- National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa; Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa
- Jason S. McLellan
- Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA
- 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, 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
-
Vol. 2,
no. 6
p. 100313
Abstract
Summary: The continual emergence of novel coronaviruses (CoV), such as severe acute respiratory syndrome-(SARS)-CoV-2, highlights the critical need for broadly reactive therapeutics and vaccines against this family of viruses. From a recovered SARS-CoV donor sample, we identify and characterize a panel of six monoclonal antibodies that cross-react with CoV spike (S) proteins from the highly pathogenic SARS-CoV and SARS-CoV-2, and demonstrate a spectrum of reactivity against other CoVs. Epitope mapping reveals that these antibodies recognize multiple epitopes on SARS-CoV-2 S, including the receptor-binding domain, the N-terminal domain, and the S2 subunit. Functional characterization demonstrates that the antibodies mediate phagocytosis—and in some cases trogocytosis—but not neutralization in vitro. When tested in vivo in murine models, two of the antibodies demonstrate a reduction in hemorrhagic pathology in the lungs. The identification of cross-reactive epitopes recognized by functional antibodies expands the repertoire of targets for pan-coronavirus vaccine design strategies.
