An alpaca-derived nanobody neutralizes the SARS-CoV-2 omicron variant
The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for anti-SARS-CoV-2 agents that are effective against emergent strains in...
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Published in | bioRxiv |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Language | English |
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Cold Spring Harbor
Cold Spring Harbor Laboratory Press
27.12.2022
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Abstract | The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for anti-SARS-CoV-2 agents that are effective against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production and potential for delivery via inhalation. Here, we characterize the RBD-specific nanobody W25, which we previously isolated from an alpaca, and show superior neutralization activity towards Omicron lineage BA.1 in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike surface glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. Furthermore, we show that W25 also binds the spike protein from the emerging, more infectious Omicron BA.2 lineage with picomolar affinity. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse prioritization of W25 for further clinical development.Competing Interest StatementThe authors have declared no competing interest. |
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AbstractList | The SARS-CoV2 Omicron variant sub-lineages spread rapidly through the world, mostly due to their immune-evasive properties. This has put a significant part of the population at risk for severe disease and underscores the need for anti-SARS-CoV-2 agents that are effective against emergent strains in vulnerable patients. Camelid nanobodies are attractive therapeutic candidates due to their high stability, ease of large-scale production and potential for delivery via inhalation. Here, we characterize the RBD-specific nanobody W25, which we previously isolated from an alpaca, and show superior neutralization activity towards Omicron lineage BA.1 in comparison to all other SARS-CoV2 variants. Structure analysis of W25 in complex with the SARS-CoV2 spike surface glycoprotein shows that W25 engages an RBD epitope not covered by any of the antibodies previously approved for emergency use. Furthermore, we show that W25 also binds the spike protein from the emerging, more infectious Omicron BA.2 lineage with picomolar affinity. In vivo evaluation of W25 prophylactic and therapeutic treatments across multiple SARS-CoV-2 variant infection models, together with W25 biodistribution analysis in mice, demonstrates favorable pre-clinical properties. Together, these data endorse prioritization of W25 for further clinical development.Competing Interest StatementThe authors have declared no competing interest. |
Author | Burger, Jorg Macloughlin, Ronan Thakur, Nazia Ida Vang Andersen Herth, Matthias Manfred Watterson, Daniel Kramer, Vasko Sara Irene Lopes Van Den Broek Song, David Bailey, Dalan Jung, James Kjaer, Andreas Jara, Ronald Jones, Martina Himelreichs, Johanna Chappell, Keith Liang, Benjamin Paramitha, Devina De Sng, Julian Jorgensen, Jesper Yorka Cheuquemilla Rojas-Fernandez, Alejandro Khromykh, Alexander A Isaacs, Ariel Chana-Cuevas, Pedro Christian Mt Spahn Mielke, Thorsten Guillermo Valenzuela Nieto Modhiran, Naphak Hewins, Peter Schwefel, David Jurado, Kellie Ann Munro, Trent Yu Shang Low Amarilla, Alberto A Young, Paul R Lauer, Simon Malte Miranda-Chacon, Zaray |
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Title | An alpaca-derived nanobody neutralizes the SARS-CoV-2 omicron variant |
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