Kim Youseong, Park In Ho, Shin Jiwoo, Choi Jaibyung, Jeon Chansol, Jeon Seonghun, Shin Jeon-Soo, Jung Hyungil
Department of Biotechnology, Yonsei University, 50 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Institute of Immunology and Immunological Diseases, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
Adv Healthc Mater. 2023 Oct;12(26):e2300889. doi: 10.1002/adhm.202300889. Epub 2023 Jul 6.
The coronavirus pandemic has accelerated 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, a dissolving microneedle (DMN) is adopted as a mucosal vaccine delivery platform to directly penetrate the sublingual site, which is rich in antigen-presenting cells (APCs) and lymphoid tissues. The sublingual dissolving microneedle (SLDMN) vaccination platform comprised a micropillar-based compartment and a 3D-printed 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-CoV-2). Furthermore, SLDMN is used to challenge transgenic mice expressing human angiotensin-converting 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 "cytokine storm" after SARS-CoV-2 infection.
冠状病毒大流行加速了下一代疫苗接种技术的发展，以应对未来的大流行疫情。黏膜疫苗接种通过诱导免疫球蛋白A（IgA）和体液IgG的分泌，有效保护病毒进入的主要部位——黏膜表面。在此，采用溶解微针（DMN）作为黏膜疫苗递送平台，直接穿透富含抗原呈递细胞（APC）和淋巴组织的舌下部位。舌下溶解微针（SLDMN）接种平台由基于微柱的隔室和作为DMN贴片替代品的3D打印SLDMN施用器组成。使用体外光学相干断层扫描（OCT）和体内组织学分析评估SLDMN的穿透效果。还使用严重急性呼吸综合征冠状病毒2（SARS-CoV-2）的重组刺突（S1）蛋白以疫苗形式评估SLDMN的效果。此外，使用SLDMN对表达人血管紧张素转换酶2（hACE2）受体的转基因小鼠进行攻毒。与肌肉注射（IM）相比，评估其对感染后抗体产生、存活率和炎症减轻的影响。总体而言，SLDMN通过IgA分泌有效诱导黏膜免疫，减轻肺部炎症，并降低细胞因子和趋化因子水平，这可能预防SARS-CoV-2感染后的“细胞因子风暴”。
