Mucosal Adjuvants Delivered by a Mucoadhesive Patch for Sublingual Administration of Subunit Vaccines

Among mucosal administration routes for vaccines, the sublingual route has been proven capable of inducing a potent systemic and mucosal immune response. However, the absence of a simple and compliant delivery system and the lack of robust mucosal adjuvants impede the development of sublingual vaccines. Here, we describe a mucoadhesive patch made of a layer-by-layer assembly of polysaccharides, chitosan, and hyaluronic acid. The mucoadhesive patch was covered by adjuvanted nanoparticles carrying viral proteins. We showed that the nanoparticles effectively cross the outer layers of the sublingual mucosa to reach the epithelium. Furthermore, the encapsulated adjuvants, 3M-052 and mifamurtide, targeting toll-like receptor (TLR) 7/8 and nucleotide-binding oligomerization domain-2 (NOD2), respectively, remain fully active after encapsulation into nanoparticles and exhibit a cytokine/chemokine signature similar to the mucosal gold-standard adjuvant, the cholera toxin. However, the particulate adjuvants induced more moderate levels of proinflammatory interleukin (IL)-6 and keratinocyte chemoattractant (KC), suggesting a controlled activation of the innate immune response.

Automated summary

This study developed a mucoadhesive patch that can effectively deliver viral proteins to the epithelium of the sublingual mucosa through mucosal administration. By encapsulating adjuvants 3M-052 and mifamurtide in nanoparticles, targeted activation of TLR-7/8 and NOD2 was achieved, showing a cytokine/chemokine signature similar to the cholera toxin during the activation of innate immune response.