A Synthetic Virus-like Assembly Unlocks Dual-Antigen Presentation for Broad-Spectrum Anti-SARS-CoV-2 Immunity | 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 A Synthetic Virus-like Assembly Unlocks Dual-Antigen Presentation for Broad-Spectrum Anti-SARS-CoV-2 Immunity Jingjing Zhang, Fengyuan Zeng, Yanmei Li, Yixuan Wang, Zhenxiao Zhang, and 25 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8859110/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 18 You are reading this latest preprint version Abstract In the present study, building on the previous development of a DC-SIGN-targeting virus-like structure (VLS) vaccine platform and a comprehensive characterization of SARS-CoV-2 structural biology, particularly insights into the role of the nucleocapsid (N) protein in eliciting cytotoxic T lymphocyte (CTL) responses during infection, we designed a SARS-CoV-2 virion-mimetic structural vaccine that encapsulates mRNA encoding the spike S1 antigen complexed with N protein complexes, with S1 proteins loaded on its surface. This characterized virion-mimetic structural vaccine not only induces high-efficiency antibodies against both spike and N proteins but also elicits robust S1-specific and N-specific CTL responses in animal models. Furthermore, the generated antibodies exhibit cross-reactive neutralizing activity against multiple SARS-CoV-2 variants and provide protective immunity against mutant viral challenge in immunized hosts. This SARS-CoV-2 virion-mimetic structure effectively recapitulates natural infection pathways, comprehensively activating the innate immune system and thereby creating an optimal microenvironment for eliciting potent and broad-spectrum adaptive immune responses. Biological sciences/Computational biology and bioinformatics Biological sciences/Immunology Biological sciences/Microbiology Virion-mimetic structure Vaccine SARS-CoV-2 Immune response CTL Full Text Additional Declarations No competing interests reported. Table 1 and 2 available in the Supplementary Files section. Supplementary Files Table.docx SupplementaryMaterials.pdf SupplementaryInfoFile.pdf Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: Revision requested 16 Apr, 2026 Reviews received at journal 16 Apr, 2026 Reviews received at journal 14 Apr, 2026 Reviews received at journal 13 Apr, 2026 Reviews received at journal 13 Apr, 2026 Reviewers agreed at journal 05 Apr, 2026 Reviewers agreed at journal 05 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviewers agreed at journal 02 Apr, 2026 Reviews received at journal 31 Mar, 2026 Reviewers agreed at journal 31 Mar, 2026 Reviewers agreed at journal 31 Mar, 2026 Reviewers agreed at journal 31 Mar, 2026 Reviewers invited by journal 31 Mar, 2026 Editor assigned by journal 30 Mar, 2026 Editor invited by journal 17 Mar, 2026 Submission checks completed at journal 28 Feb, 2026 First submitted to journal 28 Feb, 2026 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. 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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-8859110","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":615528935,"identity":"7deab219-4142-42a7-83d8-5e1da4441909","order_by":0,"name":"Jingjing Zhang","email":"","orcid":"","institution":"Shandong WeigaoLitong Biological Products Co., Ltd.,","correspondingAuthor":false,"prefix":"","firstName":"Jingjing","middleName":"","lastName":"Zhang","suffix":""},{"id":615528938,"identity":"ccfae74f-13eb-4db4-8d3f-a5408e369501","order_by":1,"name":"Fengyuan Zeng","email":"","orcid":"","institution":"Weirui Biotechnology (Kunming) Co., 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