Journal
CELL
Volume 184, Issue 11, Pages 2939-+Publisher
CELL PRESS
DOI: 10.1016/j.cell.2021.03.055
Keywords
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Categories
Funding
- Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Science (CIFMS), China [2018I2M-2-002]
- Wellcome Trust [101122/Z/13/Z, 095541/A/11/Z, 090532/Z/09/Z]
- Cancer Research UK [C375/A17721]
- UKRI MRC [MR/S007555/1, MR/N00065X/1]
- Fast Grants, Mercatus Center
- FAPEAM [005/2020]
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico [403276/2020-9]
- Inova Fiocruz/Fundacao Oswaldo Cruz (Geracao de conhecimento) [VPPCB-007-FIO-18-2-30]
- Wellcome Trust Core Award [203141/Z/16/Z]
- NIHR Oxford BRC
- UK Research and Innovation
- Coalition for Epidemic Preparedness Innovations
- National Institute for Health Research (NIHR)
- NIHR Oxford Biomedical Research Centre
- Thames Valley and South Midland's NIHR Clinical Research Network
- UK Department of Health and Social Care as part of the PITCH (Protective Immunity from T cells to Covid-19 in Health workers) Consortium
- UK Coronavirus Immunology Consortium (UK-CIC)
- Huo Family Foundation
- NIH [U19 I082360]
- CIFMS
- FAPEAM (Rede Ge-nomica de Vigilancia em Saude -REGESAM)
- Schmidt Futures
- [WT109965MA]
- MRC [MR/N00065X/1, MR/S007555/1] Funding Source: UKRI
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Ending the SARS-CoV-2 pandemic requires global vaccination. New virus strains with mutations impact antibody responses, but some variants are less resistant than others. A monoclonal antibody can neutralize different variants and partially restore neutralization potency for other public antibodies.
Terminating the SARS-CoV-2 pandemic relies upon pan-global vaccination. Current vaccines elicit neutralizing antibody responses to the virus spike derived from early isolates. However, new strains have emerged with multiple mutations, including P.1 from Brazil, B.1.351 from South Africa, and B.1.1.7 from the UK (12, 10, and 9 changes in the spike, respectively). All have mutations in the ACE2 binding site, with P.1 and B.1.351 having a virtually identical triplet (E484K, K417N/T, and N501Y), which we show confer similar increased affinity for ACE2. We show that, surprisingly, P.1 is significantly less resistant to naturally acquired or vaccine-induced antibody responses than B.1.351, suggesting that changes outside the receptor-binding domain (RBD) impact neutralization. Monoclonal antibody (mAb) 222 neutralizes all three variants despite interacting with two of the ACE2-binding sitemutations. We explain this through structural analysis and use the 222 light chain to largely restore neutralization potency to a major class of public antibodies.
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