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The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants

DOI: 10.1016/j.chom.2021.11.013 DOI Help

Authors: Chang Liu (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science Oxford Institute, University of Oxford) , Daming Zhou (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science Oxford Institute, University of Oxford) , Rungtiwa Nutalai (Wellcome Centre for Human Genetics, University of Oxford) , Helen M. E. Duyvesteyn (Wellcome Centre for Human Genetics, University of Oxford) , Aekkachai Tuekprakhon (Wellcome Centre for Human Genetics, University of Oxford) , Helen M. Ginn (Diamond Light Source) , Wanwisa Dejnirattisai (Wellcome Centre for Human Genetics, University of Oxford) , Piyada Supasa (Wellcome Centre for Human Genetics, University of Oxford) , Alexander J. Mentzer (Wellcome Centre for Human Genetics, University of Oxford; Oxford University Hospitals NHS Foundation Trust) , Beibei Wang (Wellcome Centre for Human Genetics, University of Oxford) , James Brett Case (Wellcome Centre for Human Genetics, University of Oxford) , Yuguang Zhao (Wellcome Centre for Human Genetics, University of Oxford) , Donal T. Skelly (Oxford University Hospitals NHS Foundation Trust; University of Oxford) , Rita E. Chen (Washington University School of Medicine) , Sile Ann Johnson (Oxford University Hospitals NHS Foundation Trust; University of Oxford) , Thomas G. Ritter (Oxford University Hospitals NHS Foundation Trust) , Chris Mason (Oxford University Hospitals NHS Foundation Trust) , Tariq Malik (Public Health England (PHE)) , Nigel Temperton (University of Kent and Greenwich) , Neil G. Paterson (Diamond Light Source) , Mark A. Williams (Diamond Light Source) , David R. Hall (Diamond Light Source) , Daniel K. Clare (Diamond Light Source) , Andrew Howe (Diamond Light Source) , Philip J. R. Goulder (University of Oxford) , Elizabeth E. Fry (Wellcome Centre for Human Genetics, University of Oxford) , Michael S. Diamond (Washington University School of Medicine) , Juthathip Mongkolsapaya (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science Oxford Institute, University of Oxford; Mahidol University) , Jingshan Ren (Wellcome Centre for Human Genetics, University of Oxford) , David I. Stuart (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science Oxford Institute, University of Oxford; Diamond Light Source; Instruct-ERIC) , Gavin R. Screaton (Wellcome Centre for Human Genetics, University of Oxford; Chinese Academy of Medical Science Oxford Institute, University of Oxford)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Cell Host & Microbe

State: Published (Approved)
Published: November 2021
Diamond Proposal Number(s): 27009

Open Access Open Access

Abstract: Alpha-B.1.1.7, Beta-B.1.351, Gamma-P.1 and Delta-B.1.617.2 variants of SARS-CoV-2 express multiple mutations in the spike protein (S). These may alter the antigenic structure of S, causing escape from natural or vaccine-induced immunity. Beta is particularly difficult to neutralize using serum induced by early pandemic SARS-CoV-2 strains and is most antigenically separated from Delta. To understand this, we generated 674 mAbs from Beta infected individuals and performed a detailed structure-function analysis of the 27 most potent mAbs: one binding the spike N-terminal domain (NTD), the rest the receptor binding domain (RBD). Two of these RBD-binding mAbs recognise a neutralizing epitope conserved between SARS-CoV-1 and -2, whilst 18 target mutated residues in Beta: K417N, E484K, and N501Y. There is a major response to N501Y including a public IgVH4-39 sequence, with E484K and K417N also targeted. Recognition of these key residues underscores why serum from Beta cases poorly neutralizes early pandemic and Delta viruses.

Diamond Keywords: COVID-19; Viruses

Subject Areas: Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 30/11/2021 09:34

Documents:
1-s2.0-S1931312821005199-main.pdf

Discipline Tags:

Pathogens Infectious Diseases Health & Wellbeing Structural biology Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)