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Rapid characterization of spike variants via mammalian cell surface display.
Javanmardi, Kamyab; Chou, Chia-Wei; Terrace, Cynthia I; Annapareddy, Ankur; Kaoud, Tamer S; Guo, Qingqing; Lutgens, Josh; Zorkic, Hayley; Horton, Andrew P; Gardner, Elizabeth C; Nguyen, Giaochau; Boutz, Daniel R; Goike, Jule; Voss, William N; Kuo, Hung-Che; Dalby, Kevin N; Gollihar, Jimmy D; Finkelstein, Ilya J.
  • Javanmardi K; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA. Electronic address: kjavanmardi@utexas.edu.
  • Chou CW; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Terrace CI; CCDC Army Research Laboratory-South, Austin, TX, USA.
  • Annapareddy A; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Kaoud TS; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
  • Guo Q; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Lutgens J; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Zorkic H; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Horton AP; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Gardner EC; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Nguyen G; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Boutz DR; CCDC Army Research Laboratory-South, Austin, TX, USA.
  • Goike J; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Voss WN; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Kuo HC; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA.
  • Dalby KN; Division of Chemical Biology and Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, TX, USA.
  • Gollihar JD; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA; CCDC Army Research Laboratory-South, Austin, TX, USA; Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Ins
  • Finkelstein IJ; Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712, USA; Center for Systems and Synthetic Biology, The University of Texas at Austin, Austin, TX, USA. Electronic address: ilya@finkelsteinlab.org.
Mol Cell ; 81(24): 5099-5111.e8, 2021 12 16.
Article in English | MEDLINE | ID: covidwho-1578079
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ABSTRACT
The SARS-CoV-2 spike protein is a critical component of vaccines and a target for neutralizing monoclonal antibodies (nAbs). Spike is also undergoing immunogenic selection with variants that increase infectivity and partially escape convalescent plasma. Here, we describe Spike Display, a high-throughput platform to rapidly characterize glycosylated spike ectodomains across multiple coronavirus-family proteins. We assayed ∼200 variant SARS-CoV-2 spikes for their expression, ACE2 binding, and recognition by 13 nAbs. An alanine scan of all five N-terminal domain (NTD) loops highlights a public epitope in the N1, N3, and N5 loops recognized by most NTD-binding nAbs. NTD mutations in variants of concern B.1.1.7 (alpha), B.1.351 (beta), B.1.1.28 (gamma), B.1.427/B.1.429 (epsilon), and B.1.617.2 (delta) impact spike expression and escape most NTD-targeting nAbs. Finally, B.1.351 and B.1.1.28 completely escape a potent ACE2 mimic. We anticipate that Spike Display will accelerate antigen design, deep scanning mutagenesis, and antibody epitope mapping for SARS-CoV-2 and other emerging viral threats.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 / Mammals Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Spike Glycoprotein, Coronavirus / SARS-CoV-2 / Mammals Topics: Vaccines / Variants Limits: Animals / Humans Language: English Journal: Mol Cell Journal subject: Molecular Biology Year: 2021 Document Type: Article