Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

 Meng Yuan1,†, 

1. View ORCID ProfileDeli Huang2,†, 
2. View ORCID ProfileChang-Chun D. Lee1,†, 
3. View ORCID ProfileNicholas C. Wu3,4,†, 
4. View ORCID ProfileAbigail M. Jackson1, 
5. View ORCID ProfileXueyong Zhu1, 
6. View ORCID ProfileHejun Liu1, 
7. View ORCID ProfileLinghang Peng2, 
8. View ORCID ProfileMarit J. van Gils5, 
9. View ORCID ProfileRogier W. Sanders5,6, 
10. View ORCID ProfileDennis R. Burton2,7, 
11. View ORCID ProfileS. Momsen Reincke8,9, 
12. View ORCID ProfileHarald Prüss8,9, 
13. View ORCID ProfileJakob Kreye8,9, 
14. View ORCID ProfileDavid Nemazee2, 
15. View ORCID ProfileAndrew B. Ward1, 
16. View ORCID ProfileIan A. Wilson1,10,*

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DOI: 10.1126/science.abh1139

PDF: https://scholar.google.com/scholar_url?url=https://science.sciencemag.org/content/sci/early/2021/05/19/science.abh1139.full.pdf&hl=en&sa=T&oi=ucasa&ct=ufr&ei=_HCsYK6hFIXSmAGG4qi4Cw&scisig=AAGBfm0jXOlD7abatp6zTlOKXcx0_vabGg

Abstract

Neutralizing antibodies (nAbs) elicited against the receptor-binding site (RBS) of the spike protein of wild-type SARS-CoV-2 are generally less effective against recent variants of concern. RBS residues E484, K417 and N501 are mutated in variants first described in South Africa (B.1.351) and Brazil (P.1). We analyzed their effects on ACE2 binding and K417N and E484K mutations on nAbs isolated from COVID-19 patients. Binding and neutralization of the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2), which can both bind the RBS in alternate binding modes, are abrogated by K417N, E484K, or both. These effects can be structurally explained by their extensive interactions with RBS nAbs. However, nAbs to the more conserved, cross-neutralizing CR3022 and S309 sites were largely unaffected. The results have implications for next-generation vaccines and antibody therapies.

https://science.sciencemag.org/content/early/2021/05/19/science.abh1139.full