Transport of artificial virus-like nano-carriers via m cell mediated transcytosis

Abstract

Compared with subcutaneous or intramuscular routes for vaccination, oral vaccination or vaccine delivery via gastrointestinal mucosa has tremendous potential as it is easy to administer and pain free. Robust immune responses can be triggered successfully once vaccine carried antigen reaches the mucosal associated lymphoid tissues (MALTs). However, the absence of an efficient delivery method has always been an issue for successful oral vaccine development. In our study, inspired by mammalian orthoreovirus (MRV) transport into gut mucosal lymphoid tissue via Microfold cells (M cells), artificial virus-like nanocarriers (AVNs, gold nanocages-based and hollowed silica nanospheres-based), consisting of gold nanocages/hollowed silica spheres functionalized with the σ1 protein from mammalian reovirus (MRV), were tested as an effective oral vaccine delivery vehicle utilizing M cell-mediated transcytosis pathway for effective transport of payloads. Poly-l-lysine’s role as coating material for both AVNs was also tested. Gold AVN and Silica AVN were shown to have a significantly higher transport total compared to other experimental groups across M cell incorporated mouse organoid monolayers. Thus, we proved that with σ1 protein functionalization and poly-l-lysine (PLL) coating, a potentially highly effective transport system for oral vaccines can be developed that target M cell mediated transcytosis pathway to deliver vaccines to MALTs regardless of the type of nanoparticles.