Neutralization potency of monoclonal antibodies recognizing dominant and subdominant epitopes on SARS-CoV-2 Spike is impacted by the B.1.1.7 variant.
Immunity
; 54(6): 1276-1289.e6, 2021 06 08.
Article
in English
| MEDLINE | ID: covidwho-1163900
ABSTRACT
Interaction of the SARS-CoV-2 Spike receptor binding domain (RBD) with the receptor ACE2 on host cells is essential for viral entry. RBD is the dominant target for neutralizing antibodies, and several neutralizing epitopes on RBD have been molecularly characterized. Analysis of circulating SARS-CoV-2 variants has revealed mutations arising in the RBD, N-terminal domain (NTD) and S2 subunits of Spike. To understand how these mutations affect Spike antigenicity, we isolated and characterized >100 monoclonal antibodies targeting epitopes on RBD, NTD, and S2 from SARS-CoV-2-infected individuals. Approximately 45% showed neutralizing activity, of which â¼20% were NTD specific. NTD-specific antibodies formed two distinct groups the first was highly potent against infectious virus, whereas the second was less potent and displayed glycan-dependant neutralization activity. Mutations present in B.1.1.7 Spike frequently conferred neutralization resistance to NTD-specific antibodies. This work demonstrates that neutralizing antibodies targeting subdominant epitopes should be considered when investigating antigenic drift in emerging variants.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Spike Glycoprotein, Coronavirus
/
SARS-CoV-2
/
COVID-19
/
Antibodies, Monoclonal
/
Antibodies, Viral
/
Epitopes
Type of study:
Diagnostic study
/
Experimental Studies
/
Randomized controlled trials
Topics:
Variants
Limits:
Humans
Language:
English
Journal:
Immunity
Journal subject:
Allergy and Immunology
Year:
2021
Document Type:
Article
Affiliation country:
J.immuni.2021.03.023
Similar
MEDLINE
...
LILACS
LIS