SARS-COV-2 Omicron variants conformationally escape a rare quaternary antibody binding mode.

Journal

Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179

Informations de publication

Date de publication:
11 Dec 2023
Historique:
received: 19 04 2023
accepted: 29 11 2023
medline: 12 12 2023
pubmed: 12 12 2023
entrez: 11 12 2023
Statut: epublish

Résumé

The ongoing evolution of SARS-CoV-2 into more easily transmissible and infectious variants has provided unprecedented insight into mutations enabling immune escape. Understanding how these mutations affect the dynamics of antibody-antigen interactions is crucial to the development of broadly protective antibodies and vaccines. Here we report the characterization of a potent neutralizing antibody (N3-1) identified from a COVID-19 patient during the first disease wave. Cryogenic electron microscopy revealed a quaternary binding mode that enables direct interactions with all three receptor-binding domains of the spike protein trimer, resulting in extraordinary avidity and potent neutralization of all major variants of concern until the emergence of Omicron. Structure-based rational design of N3-1 mutants improved binding to all Omicron variants but only partially restored neutralization of the conformationally distinct Omicron BA.1. This study provides new insights into immune evasion through changes in spike protein dynamics and highlights considerations for future conformationally biased multivalent vaccine designs.

Identifiants

DOI: 10.1038/s42003-023-05649-6 PMID: 38082099 PMC: PMC10713552
pubmed: 38082099
doi: 10.1038/s42003-023-05649-6
pii: 10.1038/s42003-023-05649-6
pmc: PMC10713552
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1250

Subventions

Organisme : NIGMS NIH HHS
ID : P41 GM103311
Pays : United States
Organisme : NIH HHS
ID : S10 OD030276
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI158177
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI127521
Pays : United States
Organisme : NIGMS NIH HHS
ID : R35 GM122480
Pays : United States

Informations de copyright

© 2023. The Author(s).

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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.
ORCID: 0000-0002-3665-5717

Andrew P Horton (AP)

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.
Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.
ORCID: 0000-0002-0272-4411

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.

Ling Zhou (L)

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.

Xuping Xie (X)

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
ORCID: 0000-0003-0918-016X

Hongjie Xia (H)

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
ORCID: 0000-0002-2520-7038

Pei-Yong Shi (PY)

Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, TX, USA.
ORCID: 0000-0001-5553-1616

Rebecca Renberg (R)

DEVCOM Army Research Laboratory, Biotechnology Branch, Adelphi, MD, USA.
ORCID: 0000-0003-0640-5087

Thomas H Segall-Shapiro (TH)

Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.
DEVCOM Army Research Laboratory-South, Austin, TX, USA.

Cynthia I Terrace (CI)

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

Wesley Wu (W)

Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.

Raghav Shroff (R)

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.
Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA.
DEVCOM Army Research Laboratory-South, Austin, TX, USA.

Michelle Byrom (M)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, 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.
ORCID: 0000-0001-6246-5338

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.
ORCID: 0000-0001-8808-180X

James M Musser (JM)

Antibody Discovery and Accelerated Protein Therapeutics, 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, PA, USA.
ORCID: 0000-0002-8640-254X

Vivek Kapur (V)

Department of Animal Science and the Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, PA, 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 Chemistry, The University of Texas at Austin, Austin, TX, USA.
Department of Chemical Engineering, The University of Texas at Austin, Austin, TX, USA.
Department of Oncology, Dell Medical School, The University of Texas at Austin, Austin, TX, USA.
ORCID: 0000-0002-8823-3073

Scott C Weaver (SC)

University of Texas Medical Branch, World Reference Center for Emerging Viruses and Arboviruses, Galveston, TX, USA.
ORCID: 0000-0001-8016-8556

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. drboutz@houstonmethodist.org.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. drboutz@houstonmethodist.org.
Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA. drboutz@houstonmethodist.org.
DEVCOM Army Research Laboratory-South, Austin, TX, USA. drboutz@houstonmethodist.org.
ORCID: 0000-0001-7462-4105

Jason S McLellan (JS)

Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. jmclellan@austin.utexas.edu.
ORCID: 0000-0003-3991-542X

Jimmy D Gollihar (JD)

Center for Systems and Synthetic Biology, Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. jgollihar2@houstonmethodist.org.
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX, USA. jgollihar2@houstonmethodist.org.
Antibody Discovery and Accelerated Protein Therapeutics, Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Houston Methodist Hospital, Houston, TX, USA. jgollihar2@houstonmethodist.org.
DEVCOM Army Research Laboratory-South, Austin, TX, USA. jgollihar2@houstonmethodist.org.
ORCID: 0000-0003-3957-2092

Classifications MeSH