Journal
NATURE MEDICINE
Volume 27, Issue 4, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s41591-021-01294-w
Keywords
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Funding
- NIH [75N93019C00062, 75N93019C00051, 75N93019C00074, HHSN272201400006C, HHSN272201400008C, R01 AI157155, U01 AI151810, R01 AI142759, R01 AI134907, UL1 TR001439, P30 AR073752, U01 AI151801, U01AI141990]
- Defense Advanced Research Project Agency [HR001117S0019]
- Dolly Parton COVID-19 Research Fund at Vanderbilt University, Fast Grants (Mercatus Center)
- Future Insight Prize (Merck KGaA)
- Helen Hay Whitney Foundation postdoctoral fellowship [F30 AI152327, 5T32CA009547]
- Sealy AMP
- Smith Foundation
- Kleberg Foundation
- John S. Dunn Foundation
- Amon G. Carter Foundation
- Gilson Longenbaugh Foundation
- Summerfield Robert Foundation
- Junior Faculty Development Award from the American College of Gastroenterology
- EPA Cephalosporin Early Career and Teaching Fellowship
- Townsend Jeantet Charitable Trust [1011770]
- Leona M. and Harry B. Helmsley Charitable Trust
- Barnes-Jewish Hospital Foundation
- Siteman Cancer Center grant from the National Cancer Institute of the National Institutes of Health [P30 CA091842]
- Washington University in Saint Louis' Digestive Disease Research Core from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) [P30 DK052574]
- Washington University Institute of Clinical and Translational Sciences grant from the National Center for Advancing Translational Sciences of the National Institutes of Health [UL1TR002345]
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The study analyzed antibody neutralization activity against a panel of authentic isolates and chimeric SARS-CoV-2 variants, showing significantly reduced neutralizing activity against the B.1.351 variant first identified in South Africa. Antibodies targeting the receptor-binding domain and N-terminal domain, monoclonal antibodies, convalescent sera, and mRNA vaccine-induced immune sera exhibited decreased inhibitory activity against viruses with an E484K spike mutation, suggesting a need for updated monoclonal antibodies or vaccine adjustments to prevent loss of protection against emerging variants.
A comprehensive analysis of antibody neutralization activity against a panel of authentic isolates and chimeric SARS-CoV-2 variants shows markedly diminished neutralizing activity against the variant B.1.351, first identified in South Africa. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the global COVID-19 pandemic. Rapidly spreading SARS-CoV-2 variants may jeopardize newly introduced antibody and vaccine countermeasures. Here, using monoclonal antibodies (mAbs), animal immune sera, human convalescent sera and human sera from recipients of the BNT162b2 mRNA vaccine, we report the impact on antibody neutralization of a panel of authentic SARS-CoV-2 variants including a B.1.1.7 isolate, chimeric strains with South African or Brazilian spike genes and isogenic recombinant viral variants. Many highly neutralizing mAbs engaging the receptor-binding domain or N-terminal domain and most convalescent sera and mRNA vaccine-induced immune sera showed reduced inhibitory activity against viruses containing an E484K spike mutation. As antibodies binding to spike receptor-binding domain and N-terminal domain demonstrate diminished neutralization potency in vitro against some emerging variants, updated mAb cocktails targeting highly conserved regions, enhancement of mAb potency or adjustments to the spike sequences of vaccines may be needed to prevent loss of protection in vivo.
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