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Multivariate mining...
Multivariate mining of an alpaca immune repertoire identifies potent cross-neutralizing SARS-CoV-2 nanobodies
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- Hanke, L (author)
- Karolinska Institute,Karolinska Institutet
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- Sheward, DJ (author)
- Karolinska Institute,Karolinska Institutet,University of Cape Town
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- Pankow, A (author)
- Karolinska Institute
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- Vidakovics, Laura Perez (author)
- Karolinska Institute,Karolinska Institutet
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- Karl, V (author)
- Karolinska Institute
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- Kim, C (author)
- Karolinska Institute,Karolinska Institutet
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- Urgard, E (author)
- Karolinska Institute,Karolinska Institutet
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- Smith, NL (author)
- Karolinska Institute
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- Astorga-Wells, J (author)
- Karolinska Institute
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- Ekström, Simon (author)
- Lund University,Lunds universitet,Avdelningen för Biomedicinsk teknik,Institutionen för biomedicinsk teknik,Institutioner vid LTH,Lunds Tekniska Högskola,Masspektrometri,Sektion V,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,BioMS,Forskargrupper vid Lunds universitet,Department of Biomedical Engineering,Departments at LTH,Faculty of Engineering, LTH,Mass Spectrometry,Section V,Department of Clinical Sciences, Lund,Faculty of Medicine,Lund University Research Groups
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- Coquet, JM (author)
- Karolinska Institute,Karolinska Institutet
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- McInerney, GM (author)
- Karolinska Institute,Karolinska Institutet
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- Murrell, B (author)
- Karolinska Institute,Karolinska Institutet
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(creator_code:org_t)
- American Association for the Advancement of Science (AAAS), 2022
- 2022
- English.
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In: Science advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:12, s. eabm0220-
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Abstract
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- Conventional approaches to isolate and characterize nanobodies are laborious. We combine phage display, multivariate enrichment, next-generation sequencing, and a streamlined screening strategy to identify numerous anti–severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nanobodies. We characterize their potency and specificity using neutralization assays and hydrogen/deuterium exchange mass spectrometry (HDX-MS). The most potent nanobodies bind to the receptor binding motif of the receptor binding domain (RBD), and we identify two exceptionally potent members of this category (with monomeric half-maximal inhibitory concentrations around 13 and 16 ng/ml). Other nanobodies bind to a more conserved epitope on the side of the RBD and are able to potently neutralize the SARS-CoV-2 founder virus (42 ng/ml), the Beta variant (B.1.351/501Y.V2) (35 ng/ml), and also cross-neutralize the more distantly related SARS-CoV-1 (0.46 μg/ml). The approach presented here is well suited for the screening of phage libraries to identify functional nanobodies for various biomedical and biochemical applications.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Hanke, L
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Sheward, DJ
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Pankow, A
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Vidakovics, Laur ...
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Karl, V
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Kim, C
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show more...
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Urgard, E
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Smith, NL
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Astorga-Wells, J
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Ekström, Simon
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Coquet, JM
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McInerney, GM
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Murrell, B
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Respiratory Medi ...
- Articles in the publication
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Science advances
- By the university
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Karolinska Institutet
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Lund University