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Cross-reactive coronavirus antibodies with diverse epitope specificities and Fc effector functions.
Shiakolas, Andrea R; Kramer, Kevin J; Wrapp, Daniel; Richardson, Simone I; Schäfer, Alexandra; Wall, Steven; Wang, Nianshuang; Janowska, Katarzyna; Pilewski, Kelsey A; Venkat, Rohit; Parks, Robert; Manamela, Nelia P; Raju, Nagarajan; Fechter, Emilee Friedman; Holt, Clinton M; Suryadevara, Naveenchandra; Chen, Rita E; Martinez, David R; Nargi, Rachel S; Sutton, Rachel E; Ledgerwood, Julie E; Graham, Barney S; Diamond, Michael S; Haynes, Barton F; Acharya, Priyamvada; Carnahan, Robert H; Crowe, James E; Baric, Ralph S; Morris, Lynn; McLellan, Jason S; Georgiev, Ivelin S.
  • Shiakolas AR; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Kramer KJ; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Wrapp D; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Richardson SI; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Schäfer A; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Wall S; National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa.
  • Wang N; Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
  • Janowska K; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
  • Pilewski KA; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Venkat R; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Parks R; Division of Structural Biology, Duke University School of Medicine, Durham, NC 27710, USA.
  • Manamela NP; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Raju N; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Fechter EF; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Holt CM; Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Suryadevara N; Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
  • Chen RE; National Institute for Communicable Diseases of the National Health Laboratory Service, Johannesburg 2131, South Africa.
  • Martinez DR; Antibody Immunity Research Unit, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2193, South Africa.
  • Nargi RS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Sutton RE; Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Ledgerwood JE; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Graham BS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Diamond MS; Program in Chemical and Physical Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Haynes BF; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Acharya P; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Carnahan RH; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Crowe JE; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27516, USA.
  • Baric RS; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • Morris L; Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • McLellan JS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Georgiev IS; Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Rep Med ; 2(6): 100313, 2021 06 15.
Article in English | MEDLINE | ID: covidwho-1240648
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin Fc Fragments / Spike Glycoprotein, Coronavirus / Antibodies, Monoclonal / Epitopes Type of study: Experimental Studies / Randomized controlled trials Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Cell Rep Med Year: 2021 Document Type: Article Affiliation country: J.xcrm.2021.100313

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Immunoglobulin Fc Fragments / Spike Glycoprotein, Coronavirus / Antibodies, Monoclonal / Epitopes Type of study: Experimental Studies / Randomized controlled trials Topics: Vaccines Limits: Animals / Female / Humans Language: English Journal: Cell Rep Med Year: 2021 Document Type: Article Affiliation country: J.xcrm.2021.100313