Paired heavy- and light-chain signatures contribute to potent SARS-CoV-2 neutralization in public antibody responses.
Cell Rep
; 37(1): 109771, 2021 10 05.
Article
en En
| MEDLINE
| ID: mdl-34587480
Understanding mechanisms of protective antibody recognition can inform vaccine and therapeutic strategies against SARS-CoV-2. We report a monoclonal antibody, 910-30, targeting the SARS-CoV-2 receptor-binding site for ACE2 as a member of a public antibody response encoded by IGHV3-53/IGHV3-66 genes. Sequence and structural analyses of 910-30 and related antibodies explore how class recognition features correlate with SARS-CoV-2 neutralization. Cryo-EM structures of 910-30 bound to the SARS-CoV-2 spike trimer reveal binding interactions and its ability to disassemble spike. Despite heavy-chain sequence similarity, biophysical analyses of IGHV3-53/3-66-encoded antibodies highlight the importance of native heavy:light pairings for ACE2-binding competition and SARS-CoV-2 neutralization. We develop paired heavy:light class sequence signatures and determine antibody precursor prevalence to be â¼1 in 44,000 human B cells, consistent with public antibody identification in several convalescent COVID-19 patients. These class signatures reveal genetic, structural, and functional immune features that are helpful in accelerating antibody-based medical interventions for SARS-CoV-2.
Palabras clave
Texto completo:
1
Base de datos:
MEDLINE
Asunto principal:
Glicoproteína de la Espiga del Coronavirus
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Enzima Convertidora de Angiotensina 2
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SARS-CoV-2
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COVID-19
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Anticuerpos Monoclonales
Tipo de estudio:
Prognostic_studies
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Risk_factors_studies
Límite:
Aged
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Animals
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Humans
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Male
Idioma:
En
Revista:
Cell Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos