Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants.


Journal

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

Informations de publication

Date de publication:
17 Feb 2021
Historique:
entrez: 23 2 2021
pubmed: 24 2 2021
medline: 24 2 2021
Statut: epublish

Résumé

The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.

Identifiants

pubmed: 33619487
doi: 10.1101/2021.02.16.430500
pmc: PMC7899451
pii:
doi:

Types de publication

Preprint

Langues

eng

Commentaires et corrections

Type : UpdateIn

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Auteurs

Meng Yuan (M)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Deli Huang (D)

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Chang-Chun D Lee (CD)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Nicholas C Wu (NC)

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

Abigail M Jackson (AM)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Xueyong Zhu (X)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Hejun Liu (H)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Linghang Peng (L)

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Marit J van Gils (MJ)

Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.

Rogier W Sanders (RW)

Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, Location AMC, University of Amsterdam, Amsterdam, The Netherlands.
Department of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021, USA.

Dennis R Burton (DR)

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Ragon Institute of MGH, Harvard and MIT, Cambridge, MA 02139, USA.

S Momsen Reincke (SM)

German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.

Harald Prüss (H)

German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.

Jakob Kreye (J)

German Center for Neurodegenerative Diseases (DZNE) Berlin, Berlin, Germany.
Department of Neurology and Experimental Neurology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität Berlin, and Berlin Institute of Health, Berlin, Germany.

David Nemazee (D)

Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Andrew B Ward (AB)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Ian A Wilson (IA)

Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA, 92037, USA.

Classifications MeSH