A novel self-assembled epitope peptide nanoemulsion vaccine targeting nasal mucosal epithelial cell for reinvigorating CD8+ T cell immune activity and inhibiting tumor progression.
A novel self-assembled epitope peptide nanoemulsion vaccine targeting nasal mucosal epithelial cell for reinvigorating CD8+ T cell immune activity and inhibiting tumor progression.
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DOI：
10.1016/j.ijbiomac.2021.05.158
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发表时间：
2021-05
影响因子：
8.2
通讯作者：
Yun Yang;Shuang Ge;Zhen Song;Anni Zhao;Liqun Zhao;Zhiming Hu;Dingyi Cai;Zelong Zhang;Liusheng Peng;D. Lu;Ping Luo;Weijun Zhang;Hong-wu Sun;Quanming Zou;H. Zeng
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文献类型：
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作者：
Yun Yang;Shuang Ge;Zhen Song;Anni Zhao;Liqun Zhao;Zhiming Hu;Dingyi Cai;Zelong Zhang;Liusheng Peng;D. Lu;Ping Luo;Weijun Zhang;Hong-wu Sun;Quanming Zou;H. Zeng
表位肽由于其免疫原性差和递送效率低而不适合用于鼻施用免疫。在此，我们报道了一种鼻内自组装纳米疫苗（I-OVA NE），其负载有肽IKVAV-OVA 257 -264（I-OVA）、层粘连蛋白肽（Ile-Lys-Val-ala-瓦尔，IKVAV）和OVA 257 - 264表位缀合肽。该具有浓度为4 mg/mL的I-OVA的纳米疫苗显示出30.37 ± 2.49 nm的平均粒径、-16.67 ± 1.76 mV的zeta电位和84.07 ± 7.59%的包封率。此外，粘蛋白没有改变其稳定性（大小，PdI和zeta电位）。鼻腔给药后鼻粘膜和肺组织均无明显急性病理改变。同时，I-OVANE的抗原摄取也得到促进，鼻腔滞留时间也有所延长。整合素抗体阻断后，纳米疫苗的摄取率明显高于游离I-OVA（P< 0.001），提示IKVAV与整合素的结合参与了表位肽的摄取。重要的是，这种纳米疫苗增强了表现出OVA 257 -264特异性CTL活性和Th 1免疫应答的肽特异性CD 8 +T细胞，导致在E.G7-OVA荷瘤小鼠中诱导保护性免疫。总之，这些数据表明I-OVA NE可以是肿瘤疫苗开发的适用策略。
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 OVA257–264epitope 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 prolongedin 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.