Abstract：
The delivery of vaccines plays a pivotal role in influencing the strength and longevity of the immune response and controlling reactogenicity. Mucosal immunization, as compared to parenteral vaccination, could offer greater protection against respiratory infections while being less invasive. While oral vaccination has been presumed less effective and believed to target mainly the gastrointestinal tract, trans-buccal delivery using mucoadhesive films (MAF) may allow targeted delivery to the mucosa. Here we present an effective strategy for mucosal delivery of several vaccine platforms incorporated in MAF, including DNA plasmids, viral vectors, and lipid nanoparticles incorporating mRNA (mRNA/LNP). The mRNA/LNP vaccine formulation targeting SARS-CoV-2 as a proof of concept remained stable within MAF consisting of slowly releasing water-soluble polymers and an impermeable backing layer, facilitating enhanced penetration into the oral mucosa. This formulation elicited antibody and cellular responses comparable to the intramuscular injection, but also induced the production of mucosal IgAs, highlighting its efficacy, particularly for use as a booster vaccine and the potential advantage for protection against respiratory infections. The MAF vaccine preparation demonstrates significant advantages, such as efficient delivery, stability, and simple noninvasive administration with the potential to alleviate vaccine hesitancy.
摘要：
疫苗的递送在影响免疫应答的强度和寿命以及控制反应原性方面起着关键作用。粘膜免疫，与肠胃外疫苗接种相比，可以提供更好的保护，防止呼吸道感染，同时具有较小的侵入性。虽然口服疫苗被认为效果较差，并被认为主要针对胃肠道，使用粘膜粘附膜(MAF)的经颊递送可允许靶向递送至粘膜。在这里，我们提出了一种有效的策略，用于粘膜递送纳入MAF的几种疫苗平台，包括DNA质粒,病毒载体,和掺入mRNA(mRNA/LNP)的脂质纳米颗粒。作为概念证明的针对SARS-CoV-2的mRNA/LNP疫苗制剂在由缓慢释放的水溶性聚合物和不可渗透的背衬层组成的MAF中保持稳定。促进增强渗透到口腔粘膜。该制剂引起与肌内注射相当的抗体和细胞反应。但也诱导粘膜IgA的产生，突出其功效，特别是用作加强疫苗和预防呼吸道感染的潜在优势。MAF疫苗制剂显示出显著的优势，如高效交付，稳定性,和简单的非侵入性给药，有可能减轻疫苗的犹豫。
