Structural insights into broadly neutralizing antibodies elicited by hybrid immunity against SARS-CoV-2.
Emerg Microbes Infect
; 12(1): 2146538, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-36354024
ABSTRACT
ABSTRACTIncreasing spread by SARS-CoV-2 Omicron variants challenges existing vaccines and broadly reactive neutralizing antibodies (bNAbs) against COVID-19. Here we determine the diversity, potency, breadth and structural insights of bNAbs derived from memory B cells of BNT162b2-vaccinee after homogeneous Omicron BA.1 breakthrough infection. The infection activates diverse memory B cell clonotypes for generating potent class I/II and III bNAbs with new epitopes mapped to the receptor-binding domain (RBD). The top eight bNAbs neutralize wildtype and BA.1 potently but display divergent IgH/IgL sequences and neuralization profiles against other variants of concern (VOCs). Two of them (P2D9 and P3E6) belonging to class III NAbs display comparable potency against BA.4/BA.5, although structural analysis reveals distinct modes of action. P3E6 neutralizes all variants tested through a unique bivalent interaction with two RBDs. Our findings provide new insights into hybrid immunity on BNT162b2-induced diverse memory B cells in response to Omicron breakthrough infection for generating diverse bNAbs with distinct structural basis.
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Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
SARS-CoV-2
/
COVID-19
Límite:
Humans
Idioma:
En
Revista:
Emerg Microbes Infect
Año:
2023
Tipo del documento:
Article