Synthetic repertoires derived from convalescent COVID-19 patients enable discovery of SARS-CoV-2 neutralizing antibodies and a novel quaternary binding modality.

Journal

bioRxiv : the preprint server for biology
Titre abrégé: bioRxiv
Pays: United States
ID NLM: 101680187

Informations de publication

Date de publication:
09 Apr 2021
Historique:
pubmed: 15 4 2021
medline: 15 4 2021
entrez: 14 4 2021
Statut: epublish

Résumé

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has sparked concern over the continued effectiveness of existing therapeutic antibodies and vaccines. Hence, together with increased genomic surveillance, methods to rapidly develop and assess effective interventions are critically needed. Here we report the discovery of SARS-CoV-2 neutralizing antibodies isolated from COVID-19 patients using a high-throughput platform. Antibodies were identified from unpaired donor B-cell and serum repertoires using yeast surface display, proteomics, and public light chain screening. Cryo-EM and functional characterization of the antibodies identified N3-1, an antibody that binds avidly (K

Identifiants

DOI: 10.1101/2021.04.07.438849 PMID: 33851158 PMC: PMC8043448
pubmed: 33851158
doi: 10.1101/2021.04.07.438849
pmc: PMC8043448
pii:
doi:

Types de publication

Preprint

Langues

eng

Subventions

Organisme : NIGMS NIH HHS
ID : R35 GM122480
Pays : United States

Déclaration de conflit d'intérêts

Competing Interest Statement JL, ADE, EMM, GG, and DRB declare competing financial interests in the form of provisional and granted patent applications relevant to Ig-Seq. JG, CH, ECG, AH, DRB, EMM, JSM, GCI, ADE, GG, and JDG have filed provisional applications for the discovery of neutralizing antibodies. JG, DRB, ECG, AH, and JDG have filed applications for additional methods relevant to this work.

Références

Science. 2021 Feb 19;371(6531):850-854
pubmed: 33495308
Nature. 2020 Aug;584(7819):120-124
pubmed: 32454512
Nat Methods. 2017 Mar;14(3):290-296
pubmed: 28165473
Science. 2020 Aug 7;369(6504):650-655
pubmed: 32571838
Science. 2020 Aug 21;369(6506):1014-1018
pubmed: 32540904
Immunity. 2020 Dec 15;53(6):1272-1280.e5
pubmed: 33242394
Cell Mol Immunol. 2020 Jun;17(6):613-620
pubmed: 32203189
Acta Crystallogr D Biol Crystallogr. 2002 Nov;58(Pt 11):1948-54
pubmed: 12393927
Nature. 2020 Mar;579(7798):265-269
pubmed: 32015508
Science. 2020 Aug 21;369(6506):1010-1014
pubmed: 32540901
Emerg Microbes Infect. 2020 Dec;9(1):382-385
pubmed: 32065055
Nature. 2020 Mar;579(7798):270-273
pubmed: 32015507
Science. 2020 Mar 13;367(6483):1260-1263
pubmed: 32075877
Science. 2020 Aug 28;369(6507):1119-1123
pubmed: 32661058
Cell Rep. 2021 Oct 5;37(1):109771
pubmed: 34587480
mBio. 2020 Oct 30;11(6):
pubmed: 33127862
Nature. 2020 Jul;583(7815):290-295
pubmed: 32422645
Cell Mol Immunol. 2020 Jun;17(6):621-630
pubmed: 32415260
Mol Cell. 2021 Dec 16;81(24):5099-5111.e8
pubmed: 34919820
Elife. 2018 Mar 07;7:
pubmed: 29513216
Nature. 2020 Aug;584(7821):450-456
pubmed: 32698192
Nature. 2003 Nov 27;426(6965):450-4
pubmed: 14647384
Nat Struct Mol Biol. 2020 Oct;27(10):934-941
pubmed: 32737467
Science. 2020 Sep 18;369(6510):1501-1505
pubmed: 32703906
Cell Host Microbe. 2021 Apr 14;29(4):529-539.e3
pubmed: 33705729
Nat Methods. 2015 May;12(5):380-1
pubmed: 25924071
Science. 2020 May 8;368(6491):630-633
pubmed: 32245784
Nat Med. 2015 Jan;21(1):86-91
pubmed: 25501908
Nat Struct Mol Biol. 2020 Oct;27(10):942-949
pubmed: 32753755
Stem Cell Res. 2020 Dec 15;50:102125
pubmed: 33341604
Commun Biol. 2021 Jul 15;4(1):874
pubmed: 34267316
Science. 2021 Feb 12;371(6530):
pubmed: 33436526
Science. 2021 Jun 4;372(6546):1108-1112
pubmed: 33947773
Acta Crystallogr D Biol Crystallogr. 2004 Dec;60(Pt 12 Pt 1):2126-32
pubmed: 15572765
Nat Struct Mol Biol. 2020 Oct;27(10):925-933
pubmed: 32699321
Proc Natl Acad Sci U S A. 2014 Feb 11;111(6):2259-64
pubmed: 24469811
Science. 2020 Mar 27;367(6485):1444-1448
pubmed: 32132184
Commun Biol. 2021 Feb 24;4(1):267
pubmed: 33627795
Acta Crystallogr D Struct Biol. 2018 Jun 1;74(Pt 6):519-530
pubmed: 29872003
Genome Biol. 2019 Jun 24;20(1):129
pubmed: 31234903
Nature. 2020 Dec;588(7839):682-687
pubmed: 33045718
Angew Chem Int Ed Engl. 2021 Apr 26;60(18):10273-10278
pubmed: 33684258
Cell. 2020 Aug 20;182(4):828-842.e16
pubmed: 32645326
Nat Methods. 2019 Nov;16(11):1146-1152
pubmed: 31591575
J Infect Dis. 2018 Jul 13;218(4):555-562
pubmed: 29659889
N Engl J Med. 2021 Feb 18;384(7):610-618
pubmed: 33406353
Infect Genet Evol. 2021 Sep;93:104941
pubmed: 34044192
Proc Natl Acad Sci U S A. 2004 Feb 24;101(8):2536-41
pubmed: 14983044
Protein Sci. 2018 Jan;27(1):14-25
pubmed: 28710774

Auteurs

Jule Goike (J)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Ching-Lin Hsieh (CL)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Andrew Horton (A)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Elizabeth C Gardner (EC)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Foteini Bartzoka (F)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Nianshuang Wang (N)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Kamyab Javanmardi (K)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Andrew Herbert (A)

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.

Shawn Abbassi (S)

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.

Rebecca Renberg (R)

CCDC Army Research Laboratory, Biotechnology Branch, Adelphi, MD, USA.

Michael J Johanson (MJ)

National Center for Therapeutics Manufacturing, Texas A&M University, College Station, TX, USA.

Jose A Cardona (JA)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Thomas Segall-Shapiro (T)

CCDC Army Research Laboratory-South, Austin, TX, USA.

Ling Zhou (L)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Ruth H Nissly (RH)

Department of Veterinary and Biomedical Science and Animal Diagnostic Laboratory, The Pennsylvania State University, University Park, Pennsylvania, USA.

Abhinay Gontu (A)

Department of Veterinary and Biomedical Science and Animal Diagnostic Laboratory, The Pennsylvania State University, University Park, Pennsylvania, USA.

Michelle Byrom (M)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Andre C Maranhao (AC)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Anna M Battenhouse (AM)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Varun Gejji (V)

National Center for Therapeutics Manufacturing, Texas A&M University, College Station, TX, USA.

Laura Soto-Sierra (L)

National Center for Therapeutics Manufacturing, Texas A&M University, College Station, TX, USA.
Department of Agricultural and Biological Engineering, Texas A&M University, College Station, TX, USA.

Emma R Foster (ER)

National Center for Therapeutics Manufacturing, Texas A&M University, College Station, TX, USA.
Department of Agricultural and Biological Engineering, Texas A&M University, College Station, TX, USA.

Susan L Woodard (SL)

National Center for Therapeutics Manufacturing, Texas A&M University, College Station, TX, USA.

Zivko L Nikolov (ZL)

National Center for Therapeutics Manufacturing, Texas A&M University, College Station, TX, USA.
Department of Agricultural and Biological Engineering, Texas A&M University, College Station, TX, USA.

Jason Lavinder (J)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.

Will N Voss (WN)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Ankur Annapareddy (A)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
CCDC Army Research Laboratory-South, Austin, TX, USA.

Gregory C Ippolito (GC)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.

Andrew D Ellington (AD)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.

Edward M Marcotte (EM)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Ilya J Finkelstein (IJ)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Randall A Hughes (RA)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
CCDC Army Research Laboratory-South, Austin, TX, USA.

James M Musser (JM)

Center for Molecular and Translational Human Infectious Diseases Research, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.

Suresh V Kuchipudi (SV)

Department of Veterinary and Biomedical Science and Animal Diagnostic Laboratory, The Pennsylvania State University, University Park, Pennsylvania, USA.

Vivek Kapur (V)

Department of Animal Science and the Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, USA.

George Georgiou (G)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Department of Chemistry, The University of Texas at Austin, Austin, TX, USA.
Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.

John M Dye (JM)

U.S. Army Medical Research Institute of Infectious Diseases, Frederick, MD, USA.

Daniel R Boutz (DR)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
CCDC Army Research Laboratory-South, Austin, TX, USA.

Jason S McLellan (JS)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.

Jimmy D Gollihar (JD)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, 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 Institute, Houston Methodist Hospital, Houston, TX, USA.

Classifications MeSH