Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal immunity– an observational cohort study

Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal immunity– an observational cohort study | 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 Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal immunity– an observational cohort study Susanna Dunachie, Barbara Kronsteiner, Melissa Govender, Chang Liu, and 41 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6377378/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 COVID-19 vaccines were updated to address immune escape from variants of concern (VOC). We explored the impact of ancestral/BA.1 bivalent mRNA booster vaccination (Autumn 2022) on peripheral and nasal antibody and T-cell responses to SARS-CoV-2 in 133 healthcare workers, building on previous longitudinal vaccination studies. We demonstrate that maintenance of antibody and T-cell responses up to eighteen months following the third vaccine is at least partially driven by intercurrent infection. Boosting with the bivalent vaccine increases the breadth of circulating and nasal antibodies to spike, which waned over time but was still detectable six months post-dose. T-cell responses are well maintained and highly cross-reactive to VOCs irrespective of booster vaccination. Vaccination strongly boosted nasal IgG, but this was short-lived compared to circulating antibodies. Overall, ongoing COVID-19 vaccination provides benefit, boosting immunity in individuals who have not been recently infected, but new strategies may be needed to provide longer-term nasal immunity. Biological sciences/Immunology/Vaccines Biological sciences/Immunology/Infectious diseases Full Text Additional Declarations Yes there is potential Competing Interest. The authors declare the following competing interests: L.T. has received consulting fees from MHRA and Bavarian Nordic, and speakers’ fees from Eisai Ltd, and the Primary Care Cardiovascular society. He has received consulting fees from Astrazeneca and Synairgen paid to the University of Liverpool and support for conference attendance from AstraZeneca. T.I.dS has provided consultancy services to CSL Sequiris, Synairgen and Geovax which were paid to the University of Sheffield. G.R.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. C.J.A.D. has acted on behalf of Newcastle upon Tyne Hospitals NHS Foundation Trust as an investigator on clinical trials of COVID-19 and other vaccines sponsored by Moderna, AstraZeneca, Janssen, and Valneva, receiving no personal financial renumeration. C.J.A.D. has provided consultative advice to Synairgen, with renumeration to Newcastle University. C.J.A.D. serves on data safety and monitoring boards for non-commercial clinical trials conducted by University of Oxford, for which no renumeration is provided. E.B. is a member of the UK Joint Committee of Vaccines and Immunisation (JCVI). She holds patents in HBV and HCV vaccine antigens, has consulted for Vaccitech, and has conducted vaccine studies funded by Vaccitech, Astrazeneca and NeoVac. Supplementary Files Kronsteineretal2025BivalentSupplementaryInformation.pdf 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-6377378","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":439325871,"identity":"1de30eea-195e-4a17-96e4-9499d8939dde","order_by":0,"name":"Susanna 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He has received consulting fees from Astrazeneca and Synairgen paid to the University of Liverpool and support for conference attendance from AstraZeneca. T.I.dS has provided consultancy services to CSL Sequiris, Synairgen and Geovax which were paid to the University of Sheffield. G.R.S. sits on the GSK Vaccines Scientific Advisory Board and is a founder member of RQ Biotechnology. C.J.A.D. has acted on behalf of Newcastle upon Tyne Hospitals NHS Foundation Trust as an investigator on clinical trials of COVID-19 and other vaccines sponsored by Moderna, AstraZeneca, Janssen, and Valneva, receiving no personal financial renumeration. C.J.A.D. has provided consultative advice to Synairgen, with renumeration to Newcastle University. C.J.A.D. serves on data safety and monitoring boards for non-commercial clinical trials conducted by University of Oxford, for which no renumeration is provided. E.B. is a member of the UK Joint Committee of Vaccines and Immunisation (JCVI). She holds patents in HBV and HCV vaccine antigens, has consulted for Vaccitech, and has conducted vaccine studies funded by Vaccitech, Astrazeneca and NeoVac.","formattedTitle":"Dynamic impact of bivalent COVID-19 vaccine boosters on systemic and mucosal immunity– an observational cohort study","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"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":"","lastPublishedDoi":"10.21203/rs.3.rs-6377378/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6377378/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"COVID-19 vaccines were updated to address immune escape from variants of concern (VOC). We explored the impact of ancestral/BA.1 bivalent mRNA booster vaccination (Autumn 2022) on peripheral and nasal antibody and T-cell responses to SARS-CoV-2 in 133 healthcare workers, building on previous longitudinal vaccination studies.\r\nWe demonstrate that maintenance of antibody and T-cell responses up to eighteen months following the third vaccine is at least partially driven by intercurrent infection. Boosting with the bivalent vaccine increases the breadth of circulating and nasal antibodies to spike, which waned over time but was still detectable six months post-dose. T-cell responses are well maintained and highly cross-reactive to VOCs irrespective of booster vaccination. Vaccination strongly boosted nasal IgG, but this was short-lived compared to circulating antibodies. Overall, ongoing COVID-19 vaccination provides benefit, boosting immunity in individuals who have not been recently infected, but new strategies may be needed to provide longer-term nasal immunity. 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