Rapid Identification of Neutralizing Antibodies against SARS-CoV-2 Variants by mRNA Display.
bioRxiv
; 2021 Sep 14.
Article
in En
| MEDLINE
| ID: mdl-34545362
ABSTRACT
The increasing prevalence of 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 identified a set of antibodies against SARS-CoV-2 spike (S) proteins and characterized the structures of nAbs that recognized epitopes in the S1 subunit of the S glycoprotein. These structural studies revealed distinct binding modes for several antibodies, including targeting of rare cryptic epitopes in the receptor-binding domain (RBD) of S that interacts with angiotensin- converting enzyme 2 (ACE2) to initiate infection, as well as the S1 subdomain 1. A potent ACE2-blocking nAb was further engineered 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 a promising approach for the rapid identification of nAbs that can be used in combination to combat emerging SARS-CoV-2 variants.
Full text:
1
Database:
MEDLINE
Type of study:
Diagnostic_studies
/
Risk_factors_studies
Language:
En
Journal:
BioRxiv
Year:
2021
Type:
Article