A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.
Emerg Microbes Infect
; 13(1): 2373307, 2024 Dec.
Article
em En
| MEDLINE
| ID: mdl-38953857
ABSTRACT
SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20â
ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.
Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Anticorpos Biespecíficos
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Anticorpos Neutralizantes
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Glicoproteína da Espícula de Coronavírus
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SARS-CoV-2
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COVID-19
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Anticorpos Antivirais
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Epitopos
Limite:
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article