Nano-micro Combination: Overcoming Dual Intranasal Barriers to Elicit a Comprehensive Immune Response

Intranasal immunization is of significant importance in the prevention of respiratory tract infections, given its capacity to induce immune responses in the respiratory mucosa. However, due to the unique structure and environment of the nasal cavity, intranasal immunization is confronted with the presence of both mucus and mucosal barriers, which cannot be surmounted by a single carrier to achieve an immune effect. In this study, a system of particle-in-oil-in-water (POW) was constructed to overcome the aforementioned barriers by utilizing the nano-micro composite structure and the flexible deformation of the system. Fluorescence imaging and quantitative analysis revealed that the micron-scale structure of POW facilitated robust adherence to the mucosal surface, significantly extending the nasal residence time of the antigen from 2 h (antigen-only) to 6 h. Meanwhile, the flexibility of POW increased the contact area with cells, facilitating antigen permeation and absorption through outward migration of the particles. POW ultimately showed a comprehensive and balanced immune response; in particular, it was able to induce high expression of sIgA and IgG antibodies, which were 20- and 12-fold higher than those in the antigen-only group, respectively. Additionally, the levels of cellular cytokines such as IFN-γ and IL-4 were increased by 3.8-fold and 2.53-fold, demonstrating a superior effect compared to the injection immunization method. These findings indicate that POW strengthened the synergistic protective effect of mucosal and systemic immunity and was expected to be a new type of intranasal adjuvant for vaccines.