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Design, structure a...
Design, structure and plasma binding of ancestral β-CoV scaffold antigens
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- Hueting, David A. (author)
- KTH Royal Institute of Technology,KTH,Ytbehandlingsteknik,Science for Life Laboratory, SciLifeLab
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- Schriever, Karen (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Ytbehandlingsteknik
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- Sun, Rui (author)
- Karolinska Institute
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- Vlachiotis, Stelios (author)
- Karolinska Institute
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- Zuo, Fanglei (author)
- Karolinska Institute
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- Du, Likun (author)
- Karolinska Institute
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- Persson, Helena (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Läkemedelsutveckling,Science for Life Laboratory (SciLifeLab)
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- Hofström, Camilla (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Läkemedelsutveckling,Science for Life Laboratory (SciLifeLab)
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- Ohlin, Mats (author)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,LTH profilområde: Teknik för hälsa,LTH profilområden,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,LUCC: Lund University Cancer Centre,Other Strong Research Environments,LTH Profile Area: Engineering Health,LTH Profile areas,Faculty of Engineering, LTH,Science for Life Laboratory (SciLifeLab)
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- Walldén, Karin (author)
- Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden.
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- Buggert, Marcus (author)
- Karolinska Institutet,Karolinska Institute
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- Hammarström, Lennart (author)
- Karolinska Institute
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- Marcotte, Harold (author)
- Karolinska Institute
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- Pan-Hammarström, Qiang (author)
- Karolinska Institutet,Karolinska Institute
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- Andréll, Juni (author)
- Karolinska Institute,Stockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Karolinska Institutet, Sweden,Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden.;Karolinska Inst, Dept Med Biochem & Biophys, Stockholm, Sweden.
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- Syrén, Per-Olof (author)
- KTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap
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(creator_code:org_t)
- Springer Nature, 2023
- 2023
- English.
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In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
- Related links:
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https://doi.org/10.1...
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Abstract
Subject headings
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- We report the application of ancestral sequence reconstruction on coronavirus spike protein, resulting in stable and highly soluble ancestral scaffold antigens (AnSAs). The AnSAs interact with plasma of patients recovered from COVID-19 but do not bind to the human angiotensin-converting enzyme 2 (ACE2) receptor. Cryo-EM analysis of the AnSAs yield high resolution structures (2.6–2.8 Å) indicating a closed pre-fusion conformation in which all three receptor-binding domains (RBDs) are facing downwards. The structures reveal an intricate hydrogen-bonding network mediated by well-resolved loops, both within and across monomers, tethering the N-terminal domain and RBD together. We show that AnSA-5 can induce and boost a broad-spectrum immune response against the wild-type RBD as well as circulating variants of concern in an immune organoid model derived from tonsils. Finally, we highlight how AnSAs are potent scaffolds by replacing the ancestral RBD with the wild-type sequence, which restores ACE2 binding and increases the interaction with convalescent plasma.
Subject headings
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Immunologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Immunology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Läkemedelskemi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medicinal Chemistry (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Hueting, David A ...
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Schriever, Karen
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Sun, Rui
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Vlachiotis, Stel ...
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Zuo, Fanglei
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Du, Likun
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show more...
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Persson, Helena
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Hofström, Camill ...
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Ohlin, Mats
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Walldén, Karin
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Buggert, Marcus
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Hammarström, Len ...
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Marcotte, Harold
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Pan-Hammarström, ...
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Andréll, Juni
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Syrén, Per-Olof
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Immunology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medicinal Chemis ...
- Articles in the publication
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Nature Communica ...
- By the university
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Stockholm University
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Royal Institute of Technology
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Lund University
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Karolinska Institutet