Mosaic RBD nanoparticles protect against challenge by diverse sarbecoviruses in animal models.
Science
; 377(6606): eabq0839, 2022 08 05.
Article
en En
| MEDLINE
| ID: mdl-35857620
ABSTRACT
To combat future severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and spillovers of SARS-like betacoronaviruses (sarbecoviruses) threatening global health, we designed mosaic nanoparticles that present randomly arranged sarbecovirus spike receptor-binding domains (RBDs) to elicit antibodies against epitopes that are conserved and relatively occluded rather than variable, immunodominant, and exposed. We compared immune responses elicited by mosaic-8 (SARS-CoV-2 and seven animal sarbecoviruses) and homotypic (only SARS-CoV-2) RBD nanoparticles in mice and macaques and observed stronger responses elicited by mosaic-8 to mismatched (not on nanoparticles) strains, including SARS-CoV and animal sarbecoviruses. Mosaic-8 immunization showed equivalent neutralization of SARS-CoV-2 variants, including Omicrons, and protected from SARS-CoV-2 and SARS-CoV challenges, whereas homotypic SARS-CoV-2 immunization protected only from SARS-CoV-2 challenge. Epitope mapping demonstrated increased targeting of conserved epitopes after mosaic-8 immunization. Together, these results suggest that mosaic-8 RBD nanoparticles could protect against SARS-CoV-2 variants and future sarbecovirus spillovers.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Zoonosis
/
Infecciones por Coronavirus
/
Nanopartículas
/
Anticuerpos Neutralizantes
/
Glicoproteína de la Espiga del Coronavirus
/
Betacoronavirus
/
Anticuerpos Antivirales
/
Epítopos
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
Science
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos