A novel self-assembled epitope peptide nanoemulsion vaccine targeting nasal mucosal epithelial cell for reinvigorating CD8+ T cell immune activity and inhibiting tumor progression

Yun Yang,Shuang Ge,Zhen Song,Anni Zhao,Liqun Zhao,Zhiming Hu,Dingyi Cai,Zelong Zhang,Liusheng Peng,Dongshui Lu,Ping Luo,Weijun Zhang,Hongwu Sun,Quanming Zou,Hao Zeng

doi:10.1016/j.ijbiomac.2021.05.158

Yun Yang, Shuang Ge + Show 13 more

Open Access

https://doi.org/10.1016/j.ijbiomac.2021.05.158

Copy DOI

Abstract

Epitope peptides are not suitable for nasal administration immunity due to their poor immunogenicity and low delivery efficiency. Here, we reported an intranasal self-assembled nanovaccine (I-OVA NE), which was loaded with the peptides IKVAV-OVA257–264 (I-OVA), a laminin peptide (Ile-Lys-Val-ala-Val, IKVAV) and OVA257–264 epitope conjugated peptide. 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%. Moreover, the mucin did not alter its stability (size, PdI and zeta potential). And it also had no obvious acute pathological changes neither in the nasal mucosa nor lung tissues after nasal administration. Meanwhile, the antigen uptake of I-OVA NE was promoted, and the nasal residence time was also prolonged in vivo. Besides, the uptake rate of this nanovaccine was obviously higher than that of free I-OVA (P < 0.001) after blocking by the integrin antibody, suggesting that the binding of IKVAV to integrin is involved in the epitope peptide uptake. Importantly, this nanovaccine enhanced peptide-specific CD8+T cells exhibiting OVA257–264-specific CTL activity and Th1 immune response, leading to the induction of the protective immunity in E.G7-OVA tumor-bearing mice. Overall, these data indicate that I-OVA NE can be an applicable strategy of tumor vaccine development.

Highlights

Tumors are the second leading cause of death worldwide, with approximately 15% of patients dying every year
We found that IKVAV-OVA257 − 264 (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
A nanovaccine loaded IKVAV conjugated with a major histocompatibility complex (MHC) I restricted epitope peptide of OVA(OVA257 − 264) showed good stability and had no significant toxic effects on BEAS-2B cells, mouse nasal mucosa or mouse lung tissue after nasal administration

Summary

Introduction

Tumors are the second leading cause of death worldwide, with approximately 15% of patients dying every year. The USA FDA has approved only one of prostate tumor vaccine (Sipuleucel-T) for the treatment of prostate tumors with metastatic castration resistance in patients with limited symptoms[3].Recently, a kind of vaccine was produced by encapsulating OVA protein chemically modified with MPG ΔNLS (MPG ΔNLS–OVA conjugate) in poly (lactide-co-glycolide) acid nanoparticles. These results showed that that vaccine assisted the escape of antigens from lysosomes into the cytosol, increase the amount of antigens processed in the cytosol, and subsequently enhance antigen cross-presentation via MHC-I molecules to elicit cytotoxic CD8 + T cell responses[3]. There are no reports of OVA epitope peptides chemically modified with other chemicals among tumor vaccines

Results

Discussion

Conclusion