Mesoporous Silicon Microparticles enhance robust immunity and protection against SARS-CoV-2 in mice and improves memory response in human PBMCs.

Mesoporous Silicon Microparticles enhance robust immunity and protection against SARS-CoV-2 in mice and improves memory response in human PBMCs. | 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 Research Article Mesoporous Silicon Microparticles enhance robust immunity and protection against SARS-CoV-2 in mice and improves memory response in human PBMCs. Ana López-Gómez, Irene Real-Arévalo, Elsa Mayol, Jana Ausio Cendra, and 11 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6977613/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Silica-based materials have garnered interest as adjuvants due to their capacity to potentiate immune responses. In this study, we assess the immunogenicity and protective efficacy of heteromorphous mesoporous silicon microparticles (MSMPs) as an adjuvant in the context of SARS-CoV-2 vaccination. MSMPs conjugated with the S1 subunit of the spike protein (MSMPs-S1) induced a robust and sustained humoral immune response in BALB/c mice, comparable to that elicited by aluminum-based adjuvants. Following a booster dose, MSMPs-S1 significantly increased IgG2a titers and neutralizing antibody levels, exceeding those observed with Al(OH)₃-based formulations. Moreover, MSMPs-S1 enhanced cellular immunity, as indicated by elevated IFN-γ production in CD8⁺ T cells relative to the aluminum-adjuvanted group. In k18-hACE2 transgenic mice, vaccination with MSMPs-S1 conferred protection against a lethal SARS-CoV-2 challenge, with marked reductions in viral loads in both lung and brain tissues. In vitro , stimulation of human peripheral blood mononuclear cells (PBMCs) with MSMPs-S1 led to increased IFN-γ production in CD8⁺ T cells, particularly in the presence of dendritic cells. These findings support the potential of MSMPs as an effective adjuvant capable of promoting both humoral and cellular immunity, with relevance for the development of vaccines targeting emerging viral pathogens . Vaccine Virus Cytotoxic Mesoporous Silicon Microparticles Full Text Supplementary Files SupplementaryFiguresDDTR.pptx Cite Share Download PDF Status: Posted 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-6977613","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":491825896,"identity":"102a22da-aad6-46ae-82e5-12c26e731476","order_by":0,"name":"Ana López-Gómez","email":"","orcid":"","institution":"Complutense University of Madrid: Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Ana","middleName":"","lastName":"López-Gómez","suffix":""},{"id":491825897,"identity":"d4aa8864-0b26-49d2-9ec0-d42c45993b43","order_by":1,"name":"Irene Real-Arévalo","email":"","orcid":"","institution":"Inmunotek SL","correspondingAuthor":false,"prefix":"","firstName":"Irene","middleName":"","lastName":"Real-Arévalo","suffix":""},{"id":491825898,"identity":"67a7d078-f990-45b9-8c54-b30445e76c4b","order_by":2,"name":"Elsa Mayol","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Elsa","middleName":"","lastName":"Mayol","suffix":""},{"id":491825899,"identity":"d28a33ea-f7e1-4389-872d-30b0e86075a0","order_by":3,"name":"Jana Ausio Cendra","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Jana","middleName":"Ausio","lastName":"Cendra","suffix":""},{"id":491825900,"identity":"d525d24a-3658-4087-982c-a5662fdc4ec8","order_by":4,"name":"Diego Laxalde-Fernández","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Diego","middleName":"","lastName":"Laxalde-Fernández","suffix":""},{"id":491825901,"identity":"1fc094a8-6e0e-40b1-917f-4d8d3dcd29e2","order_by":5,"name":"Pablo Nogales-Altozano","email":"","orcid":"","institution":"CISA: Centro de Investigacion en Sanidad Animal","correspondingAuthor":false,"prefix":"","firstName":"Pablo","middleName":"","lastName":"Nogales-Altozano","suffix":""},{"id":491825902,"identity":"997355b4-20c8-4ba8-8093-027d5a0325fd","order_by":6,"name":"Benigno Rivas-Pardo","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Benigno","middleName":"","lastName":"Rivas-Pardo","suffix":""},{"id":491825903,"identity":"3e467b7d-5be4-4830-98ef-300ec18362c8","order_by":7,"name":"Beatriz Amorós-Pérez","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Beatriz","middleName":"","lastName":"Amorós-Pérez","suffix":""},{"id":491825904,"identity":"d8b5d64d-e672-4e94-b027-2a30d92ee3b9","order_by":8,"name":"Beatriz Martín-Adrados","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Beatriz","middleName":"","lastName":"Martín-Adrados","suffix":""},{"id":491825905,"identity":"4f237e92-1b79-4a7f-8dae-b382aaab3de1","order_by":9,"name":"Ignacio Juárez","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Ignacio","middleName":"","lastName":"Juárez","suffix":""},{"id":491825906,"identity":"b62946ec-be0f-4d65-a033-c0b558828866","order_by":10,"name":"Álvaro Martínez-Del-Pozo","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Álvaro","middleName":"","lastName":"Martínez-Del-Pozo","suffix":""},{"id":491825907,"identity":"285718fb-de18-46ef-81dd-1003344c3280","order_by":11,"name":"Raul J. Martín-Palma","email":"","orcid":"","institution":"Universidad Autonoma de Madrid - Campus de Cantoblanco: Universidad Autonoma de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Raul","middleName":"J.","lastName":"Martín-Palma","suffix":""},{"id":491825908,"identity":"0d4704ad-5662-41ca-a8d7-f95e546d8a80","order_by":12,"name":"Noemí Sevilla","email":"","orcid":"","institution":"CISA: Centro de Investigacion en Sanidad Animal","correspondingAuthor":false,"prefix":"","firstName":"Noemí","middleName":"","lastName":"Sevilla","suffix":""},{"id":491825909,"identity":"51a296c9-03ec-4370-bcb7-53b2ab866807","order_by":13,"name":"Eduardo Martínez-Naves","email":"","orcid":"","institution":"Universidad Complutense de Madrid","correspondingAuthor":false,"prefix":"","firstName":"Eduardo","middleName":"","lastName":"Martínez-Naves","suffix":""},{"id":491825910,"identity":"4f7cabf1-6809-4f29-9da8-0b83fb3025be","order_by":14,"name":"Manuel Gómez del Moral","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAApUlEQVRIiWNgGAWjYBADOdK1GJOuJbGBaKW6/YuPbvjwZ1v6huOnExg+/CFCi9mNZ2k3Z/Dczt1wJncD48w2orScMbvNIwHUcoN3AzMvMc4Da/ljcDvdAKTlD1EOO99jdpsh4XYCWAsDG1G2sKXd7Dlw23Am0C8He4nyy/nDx278+HNbnu/42Y0PfhDjMAaJBAT7ADEaGBj4iVQ3CkbBKBgFIxgAAK7gQUkm0JAWAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0002-0642-8142","institution":"Universidad Complutense de Madrid Facultad de Medicina","correspondingAuthor":true,"prefix":"","firstName":"Manuel","middleName":"Gómez del","lastName":"Moral","suffix":""}],"badges":[],"createdAt":"2025-06-25 19:49:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6977613/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6977613/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89471019,"identity":"1cacdcad-f13e-4a9c-bb84-d0dd764f1a86","added_by":"auto","created_at":"2025-08-20 09:25:22","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1253041,"visible":true,"origin":"","legend":"","description":"","filename":"MSMPsSARSCOV2VAXdef.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6977613/v1_covered_11f38ab1-ce63-4cbd-83a3-552f1f9c69d2.pdf"},{"id":87951359,"identity":"19da208b-124d-4046-a31d-d0d8abe14e9b","added_by":"auto","created_at":"2025-07-30 17:31:43","extension":"pptx","order_by":5,"title":"","display":"","copyAsset":false,"role":"supplement","size":197577,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryFiguresDDTR.pptx","url":"https://assets-eu.researchsquare.com/files/rs-6977613/v1/6c1454f3e4c0155bfcc88e31.pptx"}],"financialInterests":"","formattedTitle":"Mesoporous Silicon Microparticles enhance robust immunity and protection against SARS-CoV-2 in mice and improves memory response in human PBMCs.","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Vaccine, Virus, Cytotoxic, Mesoporous Silicon Microparticles","lastPublishedDoi":"10.21203/rs.3.rs-6977613/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6977613/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eSilica-based materials have garnered interest as adjuvants due to their capacity to potentiate immune responses. In this study, we assess the immunogenicity and protective efficacy of heteromorphous mesoporous silicon microparticles (MSMPs) as an adjuvant in the context of SARS-CoV-2 vaccination. MSMPs conjugated with the S1 subunit of the spike protein (MSMPs-S1) induced a robust and sustained humoral immune response in BALB/c mice, comparable to that elicited by aluminum-based adjuvants. Following a booster dose, MSMPs-S1 significantly increased IgG2a titers and neutralizing antibody levels, exceeding those observed with Al(OH)₃-based formulations. Moreover, MSMPs-S1 enhanced cellular immunity, as indicated by elevated IFN-γ production in CD8⁺ T cells relative to the aluminum-adjuvanted group. In k18-hACE2 transgenic mice, vaccination with MSMPs-S1 conferred protection against a lethal SARS-CoV-2 challenge, with marked reductions in viral loads in both lung and brain tissues. \u003cem\u003eIn vitro\u003c/em\u003e, stimulation of human peripheral blood mononuclear cells (PBMCs) with MSMPs-S1 led to increased IFN-γ production in CD8⁺ T cells, particularly in the presence of dendritic cells. These findings support the potential of MSMPs as an effective adjuvant capable of promoting both humoral and cellular immunity, with relevance for the development of vaccines targeting emerging viral pathogens\u003cem\u003e.\u003c/em\u003e\u003c/p\u003e","manuscriptTitle":"Mesoporous Silicon Microparticles enhance robust immunity and protection against SARS-CoV-2 in mice and improves memory response in human PBMCs.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-30 17:31:38","doi":"10.21203/rs.3.rs-6977613/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"7825cd4c-6344-421e-b5d8-4d0f48e1ca09","owner":[],"postedDate":"July 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-08-20T09:17:12+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-30 17:31:38","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6977613","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6977613","identity":"rs-6977613","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}