A novel oral biomimetic delivery system enhancing both the mucosal and systemic immunity of influenza virus vaccine

Oral vaccines hold great promise for preventing major infectious diseases, but their development is limited by various gastrointestinal tract (GIT) barriers and the low proportion of intestinal microfold (M) cells. Here, inspired by the specific absorption pathway of dietary fat, a novel bionic intestinal lymphatic delivery system based on large mesoporous silica nanoparticles (LMSN) was developed for oral delivery of H1N1 influenza split vaccine (SV). Encouragingly, LMSN with triglyceride biomimetic structure and encapsulated by double-end palmitic acid esterified PEG (PEG-DP), namely TGLMSN@PEG-DP, exhibited high intestinal epithelium permeability and excellent lymphatic targeting ability. Additionally, TGLMSN, which acting as both antigen carrier and adjuvant, significantly enhanced the ability of SV to stimulate dendritic cells maturation. The results demonstrated that TGLMSN@PEG-DP vigorously augmented SV-induced antigen-specific systemic and mucosal immunity, compared to oral SV alone. To our knowledge, this is the first study to customize mesoporous silica nanocarriers to load SV and deliver vaccines to mesenteric lymph nodes (MLNs) mainly through the intestinal epithelium cells (IECs) pathway rather than M cells route alone. This work will not only improve the existing influenza vaccination methods, but also open up a new avenue for the design of vaccines against pathogens infected via mucosal route.