Viral and Immunological Characteristics of COVID-19 Vaccine Breakthrough Infections | 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 Viral and Immunological Characteristics of COVID-19 Vaccine Breakthrough Infections Takeshi Arashiro, Takayuki Kanno, Sho Miyamoto, Shinji Saito, and 28 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-783083/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 Since little is known about viral and host characteristics of breakthrough infections after COVID-19 vaccination, a nationwide investigation of breakthrough cases was initiated in Japan. 130 cases (90%+ received mRNA vaccines) were reported with respiratory specimens in 117 cases and sera in 68 cases. A subset of cases shed infectious virus regardless of symptom presence or viral lineages. Viral lineages for breakthrough infections matched both temporally and spatially with the circulating lineages in Japan with no novel mutations in spike receptor binding domain that may have escaped from vaccine-induced immunity were found. Anti-spike/neutralizing antibodies of breakthrough infections in the acute phase owing to vaccine-induced immunity were significantly higher than those from unvaccinated convalescent individuals but were comparable to vaccinated uninfected individuals, and followed by boosting in the convalescent phase. Symptomatic cases had low anti-spike/neutralizing antibodies in the acute phase with robust boosting in the convalescent phase, suggesting the presence of serological correlate for symptom development in COVID-19 vaccine breakthrough infections. General Microbiology Infectious Diseases Virology severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) coronavirus disease 41 2019 (COVID-19) vaccine breakthrough infection Full Text Additional Declarations There is NO Competing Interest. Supplementary Files Supplementaryinformaiton.docx Supplementaryinformationv2.pdf Supplementary Information flatSuzukiepc.pdf Editorial Policy Checklist flatSuzukirs.pdf Reporting Summary 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. 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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-783083","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":44818794,"identity":"fa432333-69a3-4960-9134-1c2646d08ef7","order_by":0,"name":"Takeshi Arashiro","email":"","orcid":"https://orcid.org/0000-0002-5215-1500","institution":"National Institute of Infectious Diseases","correspondingAuthor":false,"prefix":"","firstName":"Takeshi","middleName":"","lastName":"Arashiro","suffix":""},{"id":44818795,"identity":"9147eb74-72be-4f94-8d46-69d96a5b64cf","order_by":1,"name":"Takayuki Kanno","email":"","orcid":"","institution":"National Institute 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