Journal
STRUCTURE
Volume 29, Issue 7, Pages 655-+Publisher
CELL PRESS
DOI: 10.1016/j.str.2021.05.014
Keywords
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Funding
- NIH Common Fund Transformative High Resolution Cryo-Electron Microscopy program [U24 GM129539]
- Simons Foundation [SF349247]
- NY State Assembly
- Intramural Program of the Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH
- Brii Bioscieces
- Jack Ma Foundation
- JBP Foundation
- NIH [DP5OD023118, R21AI143407, R21AI144408]
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Emerging SARS-CoV-2 variants pose clinical concerns due to reduced neutralization by certain antibodies, but antibodies targeting specific regions may still be effective in bypassing mutations and providing potential therapeutic benefits.
Emerging SARS-CoV-2 strains, B. 1.1.7 and B.1.351, from the UK and South Africa, respectively, show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against the original wild-type virus, and are thus of clinical concern. However, the neutralization potency of two antibodies, 1-57 and 2-7, which target the receptor-binding domain (RBD) of the spike, was unaffected by these emerging strains. Here, we report cryo-EM structures of 1-57 and 2-7 in complex with spike, revealing each of these antibodies to utilize a distinct mechanism to bypass or accommodate RBD mutations. Notably, each antibody represented an immune response with recognition distinct from those of frequent antibody classes. Moreover, many epitope residues recognized by 1-57 and 2-7 were outside hotspots of evolutionary pressure for ACE2 binding and neutralizing antibody escape. We suggest the therapeutic use of antibodies, such as 1-57 and 2-7, which target less prevalent epitopes, could ameliorate issues of monoclonal antibody escape.
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