| Téléchargement | - Voir la version finale : Arsenal of nanobodies shows broad-spectrum neutralization against SARS-CoV-2 variants of concern in vitro and in vivo in hamster models (PDF, 3.6 Mio)
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| DOI | Trouver le DOI : https://doi.org/10.1038/s42003-022-03866-z |
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| Auteur | Rechercher : Rossotti, Martin A.1; Rechercher : Van Faassen, Henk1; Rechercher : Tran, Anh T.1Identifiant ORCID : https://orcid.org/0000-0003-0644-6014; Rechercher : Sheff, Joey1; Rechercher : Sandhu, Jagdeep K.1; Rechercher : Duque, Diana1; Rechercher : Hewitt, Melissa1; Rechercher : Wen, Xiaoxue1; Rechercher : Bavananthasivam, Jegarubee1Identifiant ORCID : https://orcid.org/0000-0002-0332-4823; Rechercher : Beitari, Saina1; Rechercher : Matte, Kevin; Rechercher : Laroche, Geneviève; Rechercher : Giguère, Patrick M.Identifiant ORCID : https://orcid.org/0000-0002-0695-4855; Rechercher : Gervais, Christian1; Rechercher : Stuible, Matthew1; Rechercher : Guimond, Julie1; Rechercher : Perret, Sylvie1; Rechercher : Hussack, Greg1; Rechercher : Langlois, Marc-André1Identifiant ORCID : https://orcid.org/0000-0003-4652-3029; Rechercher : Durocher, Yves1Identifiant ORCID : https://orcid.org/0000-0002-2268-4111; Rechercher : Tanha, Jamshid1Identifiant ORCID : https://orcid.org/0000-0002-5240-4598 |
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| Affiliation | - Conseil national de recherches du Canada. Thérapeutique en santé humaine
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| Format | Texte, Article |
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| Résumé | Nanobodies offer several potential advantages over mAbs for the control of SARS-CoV-2. Their ability to access cryptic epitopes conserved across SARS-CoV-2 variants of concern (VoCs) and feasibility to engineer modular, multimeric designs, make these antibody fragments ideal candidates for developing broad-spectrum therapeutics against current and continually emerging SARS-CoV-2 VoCs. Here we describe a diverse collection of 37 anti-SARS-CoV-2 spike glycoprotein nanobodies extensively characterized as both monovalent and IgG Fc-fused bivalent modalities. The nanobodies were collectively shown to have high intrinsic affinity; high thermal, thermodynamic and aerosolization stability; broad subunit/domain specificity and cross-reactivity across existing VoCs; wide-ranging epitopic and mechanistic diversity and high and broad in vitro neutralization potencies. A select set of Fc-fused nanobodies showed high neutralization efficacies in hamster models of SARS-CoV-2 infection, reducing viral burden by up to six orders of magnitude to below detectable levels. In vivo protection was demonstrated with anti-RBD and previously unreported anti-NTD and anti-S2 nanobodies. This collection of nanobodies provides a potential therapeutic toolbox from which various cocktails or multi-paratopic formats could be built to combat multiple SARS-CoV-2 variants. |
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| Date de publication | 2022-09-09 |
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| Maison d’édition | Nature Research |
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| Licence | |
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| Dans | |
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| Langue | anglais |
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| Publications évaluées par des pairs | Oui |
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| Identificateur | 3866 |
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| Exporter la notice | Exporter en format RIS |
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| Signaler une correction | Signaler une correction (s'ouvre dans un nouvel onglet) |
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| Identificateur de l’enregistrement | ee94cac8-5d64-4ff0-a0dc-aa71012bd948 |
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| Enregistrement créé | 2023-09-27 |
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| Enregistrement modifié | 2023-09-27 |
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