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Mucosal vaccination effectively protects the mucosal surfaces, the primary sites of viral entry, by inducing the secretion of immunoglobulin A (IgA) and humoral IgG. Here, a dissolving microneedle (DMN) is adopted as a mucosal vaccine delivery platform to directly penetrate the sublingual site, which is rich in antigen\u2010presenting cells (APCs) and lymphoid tissues. The sublingual dissolving microneedle (SLDMN) vaccination platform comprised a micropillar\u2010based compartment and a 3D\u2010printed SLDMN applicator as a substitute for the DMN patch. The penetration efficacy of SLDMNs is assessed using in vitro optical coherence tomography (OCT) and in vivo histological analysis. The efficacy of SLDMN is also evaluated in a vaccine form using the recombinant spike (S1) protein of the severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102). Furthermore, SLDMN is used to challenge transgenic mice expressing human angiotensin\u2010converting enzyme 2 (hACE2) receptors. Its effects are evaluated on antibody production, survival rate, and inflammation attenuation after infection compared to the intramuscular (IM) injections. Overall, SLDMN effectively induced mucosal immunity via IgA secretion, attenuated lung inflammation, and lowered the levels of cytokines and chemokines, which may prevent the \u201ccytokine storm\u201d after SARS\u2010CoV\u20102 infection.<\/jats:p>","DOI":"10.1002\/adhm.202300889","type":"journal-article","created":{"date-parts":[[2023,6,20]],"date-time":"2023-06-20T00:44:30Z","timestamp":1687221870000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Sublingual Dissolving Microneedle (SLDMN)\u2010Based Vaccine for Inducing Mucosal Immunity against SARS\u2010CoV\u20102"],"prefix":"10.1002","volume":"12","author":[{"given":"Youseong","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Biotechnology Yonsei University  50 Yonsei\u2010ro, Seodaemun\u2010gu Seoul 03722 Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In 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