Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive protection across divergent subgroups

Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive protection across divergent subgroups | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Nanoparticle display of prefusion coronavirus spike elicits S1-focused cross-reactive protection across divergent subgroups Geoffrey Hutchinson, Olubukola Abiona, Cynthia Ziwawo, Anne Werner, and 17 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-2199814/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 04 Oct, 2023 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Abstract Multivalent antigen display is a fast-growing area of interest towards broadly protective vaccines. Current nanoparticle-based vaccine candidates demonstrate the ability to confer antibody-mediated immunity against divergent strains of notably mutable viruses. In coronaviruses, this work is predominantly aimed at targeting conserved epitopes of the receptor-binding domain. However, targeting other conserved non-RBD epitopes could further limit the potential for antigenic escape. To further explore new potential targets, we engineered protein nanoparticles displaying CoV_S-2P trimers derived from MERS-CoV, SARS-CoV-1, SARS-CoV-2, hCoV-HKU1, and hCoV-OC43 and assessed their immunogenicity in mice. Monotypic SARS-1_S-2P nanoparticles elicited cross-neutralizing antibodies against MERS_S and protected against MERS-CoV challenge. MERS and SARS-I53_dn5 nanoparticles elicited S1-focused antibodies, revealing a conserved site on the NTD. Moreover, mosaic nanoparticles co-displaying distinct CoV_S-2P trimers elicited antibody responses to distant cross-group antigens while protecting against MERS challenge despite diminished valency of MERS_S-2P. Our findings will inform further efforts towards the development of pan-coronavirus vaccines. Biological sciences/Immunology/Vaccines/Protein vaccines Biological sciences/Microbiology/Virology/SARS-CoV-2 Biological sciences/Biotechnology/Molecular engineering/Protein design Biological sciences/Biotechnology/Applied immunology/Vaccines/Protein vaccines Biological sciences/Microbiology/Virology/SARS virus Full Text Additional Declarations Yes there is potential Competing Interest. The authors declare the existence of financial and non-financial competing interests. Supplementary Files 20221024anonymousCoVdn5SupplementalsManuscriptNatureCommunicationsv8submission.docx Supplementary Dataset 1 20221103nrreportingsummaryNCOMMS22426256.pdf Reporting Summary Cite Share Download PDF Status: Published Journal Publication published 04 Oct, 2023 Read the published version in Nature Communications → Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-2199814","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":150188965,"identity":"f74a4699-0b20-4bde-9418-fa16cf0c615c","order_by":0,"name":"Geoffrey Hutchinson","email":"","orcid":"","institution":"University of Washington","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Geoffrey","middleName":"","lastName":"Hutchinson","suffix":""},{"id":150188966,"identity":"d81bfca0-06f5-4e59-9357-766ade934219","order_by":1,"name":"Olubukola Abiona","email":"","orcid":"","institution":"Case Western Reserve 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