Rational development of a human antibody cocktail that deploys multiple functions to confer Pan-SARS-CoVs protection.
Cell Res
; 31(1): 25-36, 2021 01.
Article
em En
| MEDLINE
| ID: mdl-33262452
ABSTRACT
Structural principles underlying the composition and synergistic mechanisms of protective monoclonal antibody cocktails are poorly defined. Here, we exploited antibody cooperativity to develop a therapeutic antibody cocktail against SARS-CoV-2. On the basis of our previously identified humanized cross-neutralizing antibody H014, we systematically analyzed a fully human naive antibody library and rationally identified a potent neutralizing antibody partner, P17, which confers effective protection in animal model. Cryo-EM studies dissected the nature of the P17 epitope, which is SARS-CoV-2 specific and distinctly different from that of H014. High-resolution structure of the SARS-CoV-2 spike in complex with H014 and P17, together with functional investigations revealed that in a two-antibody cocktail, synergistic neutralization was achieved by S1 shielding and conformational locking, thereby blocking receptor attachment and viral membrane fusion, conferring high potency as well as robustness against viral mutation escape. Furthermore, cluster analysis identified a hypothetical 3rd antibody partner for further reinforcing the cocktail as pan-SARS-CoVs therapeutics.
Texto completo:
1
Coleções:
01-internacional
Contexto em Saúde:
1_ASSA2030
/
4_TD
Base de dados:
MEDLINE
Assunto principal:
Anticorpos Neutralizantes
/
Anticorpos de Cadeia Única
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SARS-CoV-2
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COVID-19
/
Anticorpos Antivirais
/
Epitopos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Res
Ano de publicação:
2021
Tipo de documento:
Article