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  • Hueting, David A.KTH Royal Institute of Technology,KTH,Ytbehandlingsteknik,Science for Life Laboratory, SciLifeLab (author)

Design, structure and plasma binding of ancestral β-CoV scaffold antigens

  • Article/chapterEnglish2023

Publisher, publication year, extent ...

  • Springer Nature,2023
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:su-226056
  • https://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-226056URI
  • https://doi.org/10.1038/s41467-023-42200-xDOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-343082URI
  • https://lup.lub.lu.se/record/611b562d-327f-4bab-b473-e797ded3a94dURI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:154665022URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • QC 20240206
  • 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 and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Schriever, KarenKTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Ytbehandlingsteknik(Swepub:kth)u1buhd34 (author)
  • Sun, RuiKarolinska Institute (author)
  • Vlachiotis, SteliosKarolinska Institute (author)
  • Zuo, FangleiKarolinska Institute (author)
  • Du, LikunKarolinska Institute (author)
  • Persson, HelenaKTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Läkemedelsutveckling,Science for Life Laboratory (SciLifeLab)(Swepub:kth)u1l700sh (author)
  • Hofström, CamillaKTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Läkemedelsutveckling,Science for Life Laboratory (SciLifeLab)(Swepub:kth)u12237py (author)
  • Ohlin, MatsLund 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)(Swepub:lu)immt-moh (author)
  • Walldén, KarinStockholms universitet,Institutionen för biokemi och biofysik,Science for Life Laboratory (SciLifeLab),Stockholm Univ, Dept Biochem & Biophys, Sci Life Lab, Stockholm, Sweden.(Swepub:su)kwall (author)
  • Buggert, MarcusKarolinska Institutet,Karolinska Institute (author)
  • Hammarström, LennartKarolinska Institute (author)
  • Marcotte, HaroldKarolinska Institute (author)
  • Pan-Hammarström, QiangKarolinska Institutet,Karolinska Institute (author)
  • Andréll, JuniKarolinska 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.(Swepub:su)juand (author)
  • Syrén, Per-OlofKTH Royal Institute of Technology,KTH,Science for Life Laboratory, SciLifeLab,Proteinvetenskap(Swepub:kth)u1ewlo1g (author)
  • KTHYtbehandlingsteknik (creator_code:org_t)

Related titles

  • In:Nature Communications: Springer Nature14:12041-1723

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