Oil-in-ionic liquid nanoemulsion-based intranasal delivery system for influenza split-virus vaccine

Effective antigen delivery and immune stimulation in nasal mucosa determine the success of mucosal immunity. Here, an oil-in-ionic liquid (o/IL) nanoemulsion formulated with choline and niacin IL ([Cho][Nic]), squalene, and Tween 80 surfactant is explored as a vaccine delivery system for intranasal mucosal immunization. Compared to the o/w emulsion counterpart without the ILs, the o/IL manoemulsion showed a reduced and more uniform size of approximately 168 nm and significantly improved stability. Studies in mice model showed that when was used as an intranasal vaccine delivery system for influenza split-virus antigens, the antigens in the o/IL nanoemulsion induced strong mucosal immune responses with secretory IgA titers 25- and 5.8-fold higher than those of naked and commercial MF59-adjuvanted antigens, respectively. The o/IL nanoemulsion system also induced stronger systemic humoral responses. The excellent mucosal adjuvant effects of the o/IL nanoemulsion mainly benefited from the prolonged retention of antigens in the nasal cavity, enhanced antigen permeation into the submucosa, and the consequently promoted proliferation of CD11b cells and CD4⁺ T cells in nasal mucosa-associated lymphoid tissue. Moreover, when used as an injection adjuvant, the o/IL nanoemulsion also induced stronger humoral immune responses than MF59. Thus, the [Cho][Nic]-based o/IL nanoemulsion vaccine delivery system can serve as a promising adjuvant platform.