Rapid identification of neutralizing antibodies against SARS-CoV-2 variants by mRNA display.
Cell Rep
; 38(6): 110348, 2022 02 08.
Article
in English
| MEDLINE | ID: covidwho-1712500
ABSTRACT
The increasing prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with the ability to escape existing humoral protection conferred by previous infection and/or immunization necessitates the discovery of broadly reactive neutralizing antibodies (nAbs). Utilizing mRNA display, we identify a set of antibodies against SARS-CoV-2 spike (S) proteins and characterize the structures of nAbs that recognize epitopes in the S1 subunit of the S glycoprotein. These structural studies reveal distinct binding modes for several antibodies, including the targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interact with angiotensin-converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. Further, we engineer a potent ACE2-blocking nAb to sustain binding to S RBD with the E484K and L452R substitutions found in multiple SARS-CoV-2 variants. We demonstrate that mRNA display is an approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Observational study
Topics:
Variants
Language:
English
Journal:
Cell Rep
Year:
2022
Document Type:
Article
Affiliation country:
J.celrep.2022.110348
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