2. Academic Validation
  3. A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope

A potently neutralizing SARS-CoV-2 antibody inhibits variants of concern by utilizing unique binding residues in a highly conserved epitope

  • Immunity. 2021 Oct 12;54(10):2399-2416.e6. doi: 10.1016/j.immuni.2021.08.016.
Laura A VanBlargan 1,  Lucas J Adams 2,  Zhuoming Liu 3,  Rita E Chen 4,  Pavlo Gilchuk 5,  Saravanan Raju 4,  Brittany K Smith 2,  Haiyan Zhao 2,  James Brett Case 1,  Emma S Winkler 4,  Bradley M Whitener 1,  Lindsay Droit 3,  Ishmael D Aziati 1,  Traci L Bricker 1,  Astha Joshi 1,  Pei-Yong Shi 6,  Adrian Creanga 7,  Amarendra Pegu 7,  Scott A Handley 2,  David Wang 3,  Adrianus C M Boon 8,  James E Crowe Jr 5,  Sean P J Whelan 3,  Daved H Fremont 9,  Michael S Diamond 10
Affiliations

Affiliations

  • 1 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 2 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 3 Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 4 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 5 Vanderbilt Vaccine Center, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
  • 6 Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX 77555, USA; Departments of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA; Sealy Institute for Vaccine Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA.
  • 7 Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • 8 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • 9 Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Biochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, MO 63110, USA; Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: [email protected].
  • 10 Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology & Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: [email protected].
PMID: 34481543 DOI: 10.1016/j.immuni.2021.08.016
Abstract

With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with increased transmissibility and potential resistance, antibodies and vaccines with broadly inhibitory activity are needed. Here, we developed a panel of neutralizing anti-SARS-CoV-2 monoclonal antibodies (mAbs) that bound the receptor binding domain of the spike protein at distinct epitopes and blocked virus attachment to its host receptor, human angiotensin converting enzyme-2 (hACE2). Although several potently neutralizing mAbs protected K18-hACE2 transgenic mice against Infection caused by ancestral SARS-CoV-2 strains, Others induced escape variants in vivo or lost neutralizing activity against emerging strains. One mAb, SARS2-38, potently neutralized all tested SARS-CoV-2 variants of concern and protected mice against challenge by multiple SARS-CoV-2 strains. Structural analysis showed that SARS2-38 engaged a conserved epitope proximal to the receptor binding motif. Thus, treatment with or induction of neutralizing antibodies that bind conserved spike epitopes may limit the loss of potency of therapies or vaccines against emerging SARS-CoV-2 variants.

Keywords

SARS-CoV-2; neutralizing antibodies; variants of concern.

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