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Design, structure and plasma binding of ancestral ß-CoV scaffold antigens.
Hueting, David; Schriever, Karen; Sun, Rui; Vlachiotis, Stelios; Zuo, Fanglei; Du, Likun; Persson, Helena; Hofström, Camilla; Ohlin, Mats; Walldén, Karin; Buggert, Marcus; Hammarström, Lennart; Marcotte, Harold; Pan-Hammarström, Qiang; Andréll, Juni; Syrén, Per-Olof.
Afiliación
  • Hueting D; School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Schriever K; School of Engineering Sciences in Chemistry, Biotechnology and Health, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Sun R; School of Engineering Sciences in Chemistry, Biotechnology and Health, Department of Fibre and Polymer Technology, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Vlachiotis S; School of Engineering Sciences in Chemistry, Biotechnology and Health, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Zuo F; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Du L; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Persson H; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Hofström C; Division of Immunology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
  • Ohlin M; School of Engineering Sciences in Chemistry, Biotechnology and Health, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Walldén K; Drug Discovery and Development Platform, Science for Life Laboratory, Solna, Sweden.
  • Buggert M; School of Engineering Sciences in Chemistry, Biotechnology and Health, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Hammarström L; Drug Discovery and Development Platform, Science for Life Laboratory, Solna, Sweden.
  • Marcotte H; Drug Discovery and Development Platform, Science for Life Laboratory, Solna, Sweden.
  • Pan-Hammarström Q; Department of Immunotechnology, Lund University, Lund, Sweden.
  • Andréll J; Department of Biochemistry and Biophysics, Science for Life Laboratory, Stockholm University, Stockholm, Sweden.
  • Syrén PO; Center for Infectious Disease, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden.
Nat Commun ; 14(1): 6527, 2023 10 16.
Article en En | MEDLINE | ID: mdl-37845250
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enzima Convertidora de Angiotensina 2 / COVID-19 Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enzima Convertidora de Angiotensina 2 / COVID-19 Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2023 Tipo del documento: Article País de afiliación: Suecia Pais de publicación: Reino Unido