Sublingual Dissolving Microneedle (SLDMN)-based Vaccine For Inducing Mucosal Immunity Against SARS-CoV-2.

The coronavirus pandemic accelerates the development of next-generation vaccination technology to combat future pandemic outbreaks. 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, w e adopted a dissolving microneedle (DMN) as a mucosal vaccine delivery platform to directly penetrate the sublingual site, which is rich in antigen-presenting cells (APCs) and lymphoid tissues. O ur sublingual dissolving microneedle (SLDMN) vaccination platform comprised a micropillar-based compartment and a 3D-printed SLDMN applicator as a substitute for the DMN patch. W e assessed the penetration efficacy of SLDMNs using in vitro optical coherence tomography (OCT) and in vivo histological analysis. W e also evaluated the efficacy of SLDMN in a vaccine form using the recombinant spike (S1) protein of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furthermore, w e used SLDMN to challenge transgenic mice expressing human angiotensin-converting enzyme 2 (hACE2) receptors. W e evaluated its effects 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 might prevent the "cytokine storm" after SARS-CoV-2 infection. This article is protected by copyright. All rights reserved.