| Download | - View final version: 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 MiB)
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| DOI | Resolve DOI: https://doi.org/10.1038/s42003-022-03866-z |
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| Author | Search for: Rossotti, Martin A.1; Search for: Van Faassen, Henk1; Search for: Tran, Anh T.1ORCID identifier: https://orcid.org/0000-0003-0644-6014; Search for: Sheff, Joey1; Search for: Sandhu, Jagdeep K.1; Search for: Duque, Diana1; Search for: Hewitt, Melissa1; Search for: Wen, Xiaoxue1; Search for: Bavananthasivam, Jegarubee1ORCID identifier: https://orcid.org/0000-0002-0332-4823; Search for: Beitari, Saina1; Search for: Matte, Kevin; Search for: Laroche, Geneviève; Search for: Giguère, Patrick M.ORCID identifier: https://orcid.org/0000-0002-0695-4855; Search for: Gervais, Christian1; Search for: Stuible, Matthew1; Search for: Guimond, Julie1; Search for: Perret, Sylvie1; Search for: Hussack, Greg1; Search for: Langlois, Marc-André1ORCID identifier: https://orcid.org/0000-0003-4652-3029; Search for: Durocher, Yves1ORCID identifier: https://orcid.org/0000-0002-2268-4111; Search for: Tanha, Jamshid1ORCID identifier: https://orcid.org/0000-0002-5240-4598 |
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| Affiliation | - National Research Council of Canada. Human Health Therapeutics
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| Format | Text, Article |
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| Abstract | 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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| Publication date | 2022-09-09 |
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| Publisher | Nature Research |
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| Licence | |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| Identifier | 3866 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | ee94cac8-5d64-4ff0-a0dc-aa71012bd948 |
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| Record created | 2023-09-27 |
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| Record modified | 2023-09-27 |
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