A Novel Self-Assembled Epitope Peptide Nanoemulsion Vaccine with Targeting the Nasal Mucosal Epithelial Cell for Reinvigorating CD8+ T cell Immune Activity and Inhibiting Tumor Progression

Abstract Synthetic epitope peptide are not suitable for nasal administration due to its weak immunogenic and low delivery efficiency. In this work, we developed a intranasal epitope nanovaccine (I-OVA NE) which can prolong mucosal retention and enhance CTL activity induced by epitopes. I-OVA NE was a nanoemulsion system that assembled with IKVAV-OVA 257-264 (I-OVA) conjugated peptides.This nanovaccine with I-OVA at a concentration of 4 mg/mL showed the average particle size of 30.37±2.49 nm, zeta potential of -16.67±1.76 mV, and encapsulation rate of 84.07±7.59%. I-OVA NE particles exhibit smooth and spherical surfaces, good dispersibility and no obvious aggregation. Moreover, the physicochemical characteristics (size, PdI and zeta potential) of this vaccine did not significantly change in the condition of mucin exist. I-OVA NE had no significant cytotoxic effects on BEAS-2B cells, and no obvious acute pathological changes were observed on nasal mucosa or lung tissue in the mice after nasal immunization. We found that I-OVA NE prolonged the nasal residence time, promoted the cellular uptake of the epitope peptide and improved the antigen uptake efficiency of BEAS-2B cells, but this effect was significantly decreased after integrin blockade. Importantly, the level of Th1 cytokines and the proportion of epitope-specific CD8+ T cells increased significantly, and thus I-OVA NE protected E.G7/OVA tumor-bearing mice by suppressing tumour growth and provoking anti-tumour immune activation. Overall, these data indicate that I-OVA NE can be an applicable strategy for tumor vaccine design.