1. The antibody response to SARS-CoV-2 Beta underscores the antigenic distance to other variants
- Author
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Thomas G Ritter, Juthathip Mongkolsapaya, Beibei Wang, Alexander J. Mentzer, Daniel K. Clare, Neil G. Paterson, Donal T. Skelly, Elizabeth E. Fry, Andy G. Howe, Nigel Temperton, Jingshan Ren, Piyada Supasa, Helen M. Ginn, Helen M. E. Duyvesteyn, S A Johnson, David I. Stuart, Tariq Malik, Wanwisa Dejnirattisai, Aekkachai Tuekprakhon, D. Zhou, Michael S. Diamond, Gavin R. Screaton, David R. Hall, Philip J. R. Goulder, Rita E. Chen, R Nutalai, Chris Jb Mason, Mark A. Williams, James Brett Case, Yuguang Zhao, and Chang Liu
- Subjects
Male ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Mice, Transgenic ,Biology ,Antibodies, Viral ,Microbiology ,Article ,Antigenic distance ,Mice ,Antigen ,Neutralization Tests ,Immunity ,Virology ,Chlorocebus aethiops ,Animals ,Humans ,Beta (finance) ,Vero Cells ,Cells, Cultured ,QR355 ,SARS-CoV-2 ,Antibodies, Monoclonal ,COVID-19 ,Spike Protein ,Antibodies, Neutralizing ,Neutralizing epitope ,HEK293 Cells ,Antibody response ,Antibody Formation ,Spike Glycoprotein, Coronavirus ,Female ,Parasitology ,Protein Binding - 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., Graphical Abstract, Liu et al. generated 674 antibodies from patients infected with the SARS-CoV-2 Beta variant. 18 out of 27 most potent neutralizing antibodies isolated target the 3 mutations present in the receptor binding domain of this variant. This underscores the poor neutralization by Beta serum of early pandemic and Delta viruses.
- Published
- 2021