Journal
CELL HOST & MICROBE
Volume 30, Issue 1, Pages 53-+Publisher
CELL PRESS
DOI: 10.1016/j.chom.2021.11.013
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Funding
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China [2018-I2M-2-002]
- Wellcome Trust [101122/Z/13/Z, 090532/Z/09/Z, 203141/Z/16/Z]
- UKRI MRC [MR/N00065X/1]
- Helen Hay Whitney Foundation postdoctoral fellowship
- NIH [R01 AI157155]
- Defense Advanced Research Project Agency [HR001117S0019]
- Schmidt Futures
- Red Avenue Foundation
- Oak Foundation
- NIHR Oxford BRC
- UK Department of Health & Social Care, PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium
- UK Coronavirus Immunology Consortium (UK-CIC)
- Hyde Family Foundation
- Wellcome Trust [101122/Z/13/Z] Funding Source: Wellcome Trust
- MRC [MR/N00065X/1] Funding Source: UKRI
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This study investigated several variants of SARS-CoV-2 and found that the Beta variant has the largest antigenic difference compared to other variants, such as Delta, and is poorly neutralized by serum from early pandemic and Delta viruses. The study also revealed that certain antibodies can recognize conserved neutralizing epitopes, while others target specific mutated residues in the Beta variant.
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 recognize a neutralizing epitope conserved between SARS-CoV-1 and-2, while 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.
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