Epistasis lowers the genetic barrier to SARS-CoV-2 neutralizing antibody escape.
Nat Commun
; 14(1): 302, 2023 01 19.
Article
in En
| MEDLINE
| ID: mdl-36653360
ABSTRACT
Waves of SARS-CoV-2 infection have resulted from the emergence of viral variants with neutralizing antibody resistance mutations. Simultaneously, repeated antigen exposure has generated affinity matured B cells, producing broadly neutralizing receptor binding domain (RBD)-specific antibodies with activity against emergent variants. To determine how SARS-CoV-2 might escape these antibodies, we subjected chimeric viruses encoding spike proteins from ancestral, BA.1 or BA.2 variants to selection by 40 broadly neutralizing antibodies. We identify numerous examples of epistasis, whereby in vitro selected and naturally occurring substitutions in RBD epitopes that do not confer antibody resistance in the Wuhan-Hu-1 spike, do so in BA.1 or BA.2 spikes. As few as 2 or 3 of these substitutions in the BA.5 spike, confer resistance to nearly all of the 40 broadly neutralizing antibodies, and substantial resistance to plasma from most individuals. Thus, epistasis facilitates the acquisition of resistance to antibodies that remained effective against early omicron variants.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Antibodies, Neutralizing
/
COVID-19
Limits:
Humans
Language:
En
Journal:
Nat Commun
Year:
2023
Document type:
Article