Cross-reactive SARS-CoV-2 epitope targeted across donors informs immunogen design.
Cell Rep Med
; 3(12): 100834, 2022 12 20.
Article
en En
| MEDLINE
| ID: mdl-36423634
ABSTRACT
The emergence of the antigenically distinct and highly transmissible Omicron variant highlights the possibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune escape due to viral evolution. This continued evolution, along with the possible introduction of new sarbecoviruses from zoonotic reservoirs, may evade host immunity elicited by current SARS-CoV-2 vaccines. Identifying cross-reactive antibodies and defining their epitope(s) can provide templates for rational immunogen design strategies for next-generation vaccines. Here, we characterize the receptor-binding-domain-directed, cross-reactive humoral repertoire across 10 human vaccinated donors. We identify cross-reactive antibodies from diverse gene rearrangements targeting two conserved receptor-binding domain epitopes. An engineered immunogen enriches antibody responses to one of these conserved epitopes in mice with pre-existing SARS-CoV-2 immunity; elicited responses neutralize SARS-CoV-2, variants, and related sarbecoviruses. These data show how immune focusing to a conserved epitope targeted by human cross-reactive antibodies may guide pan-sarbecovirus vaccine development, providing a template for identifying such epitopes and translating to immunogen design.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
SARS-CoV-2
/
COVID-19
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep Med
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos