Ultrapotent neutralizing antibodies against SARS-CoV-2 with a high degree of mutation resistance.
J Clin Invest
; 132(4)2022 Feb 15.
Artículo
en Inglés
| MEDLINE | ID: covidwho-1705312
ABSTRACT
Many SARS-CoV-2 neutralizing antibodies (nAbs) lose potency against variants of concern. In this study, we developed 2 strategies to produce mutation-resistant antibodies. First, a yeast library expressing mutant receptor binding domains (RBDs) of the spike protein was utilized to screen for potent nAbs that are least susceptible to viral escape. Among the candidate antibodies, P5-22 displayed ultrahigh potency for virus neutralization as well as an outstanding mutation resistance profile. Additionally, P14-44 and P15-16 were recognized as mutation-resistant antibodies with broad betacoronavirus neutralization properties. P15-16 has only 1 binding hotspot, which is K378 in the RBD of SARS-CoV-2. The crystal structure of the P5-22, P14-44, and RBD ternary complex clarified the unique mechanisms that underlie the excellent mutation resistance profiles of these antibodies. Secondly, polymeric IgG enhanced antibody avidity by eliminating P5-22's only hotspot, residue F486 in the RBD, thereby potently blocking cell entry by mutant viruses. Structural and functional analyses of antibodies screened using both potency assays and the yeast RBD library revealed rare, ultrapotent, mutation-resistant nAbs against SARS-CoV-2.
Palabras clave
Texto completo:
Disponible
Colección:
Bases de datos internacionales
Base de datos:
MEDLINE
Asunto principal:
Anticuerpos ampliamente neutralizantes
/
SARS-CoV-2
/
COVID-19
/
Anticuerpos Antivirales
Tipo de estudio:
Ensayo controlado aleatorizado
Tópicos:
Variantes
Límite:
Animales
/
Humanos
Idioma:
Inglés
Año:
2022
Tipo del documento:
Artículo
País de afiliación:
JCI154987
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