Center for Infectious Diseases Control (CIDC), Sichuan Agricultural University, Chengdu 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China; Center for Sustainable Antimicrobials, Department of Pharmacy, Sichuan Agricultural University, Chengdu 611130, China.
Key Laboratory of Animal Disease and Human Health of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
Int J Biol Macromol. 2024 Jul;273(Pt 1):133008. doi: 10.1016/j.ijbiomac.2024.133008. Epub 2024 Jun 7.
The mucosal barrier and scavenging effect of the mucosal layer are two main obstacles in inducing mucosal immunization. To overcome these obstacles, we synthesized a bio-inspired mucoadhesive material, chitosan-catechol (ChiC), for surface modification of inactive porcine epidemic diarrhea virus (PEDV). Studies have revealed that PEDV particles can be facilely and mildly modified by Chi-C forming Chi-C-PEDV nanoparticles (Chic-Ps) through the covalent and electrostatic bond, which effectively prolongs the retention time of PEDV in the nasal mucosa. The cell co-culture model demonstrated that Chic-Ps exhibit enhanced recruitment of dendritic cells via the secretion of stimulating chemokine CCL20 and improving antigen permeability by disruption the distribution of ZO-1 protein in epithelial cells. Additionally, the flow cytometry (FCM) analysis revealed that Chic-Ps facilitate trafficking to lymph nodes and induce stronger cellular and humoral immune responses compared to unmodified PEDV. Notably, Chic-Ps induced a higher level of PEDV neutralizing antibody was induced by Chic-Ps in the nasal washes, as confirmed by a plaque reduction neutralization test. These results demonstrate that Chi-C is a promising nasal delivery system for vaccines. Proof of principle was obtained for inactivated PEDV, but similar delivery mechanisms could be applied in other vaccines when intranasal administration is needed.
黏膜屏障和黏膜层的清除作用是诱导黏膜免疫的两个主要障碍。为了克服这些障碍，我们合成了一种仿生黏附材料壳聚糖-儿茶素（ChiC），用于非活性猪流行性腹泻病毒（PEDV）的表面修饰。研究表明，PEDV 颗粒可以通过 Chi-C 轻易且温和地修饰，通过共价和静电键形成 Chi-C-PEDV 纳米颗粒（Chic-Ps），从而有效延长 PEDV 在鼻黏膜中的保留时间。细胞共培养模型表明，Chic-Ps 通过分泌刺激趋化因子 CCL20 增强树突状细胞的募集，并通过破坏上皮细胞中 ZO-1 蛋白的分布来提高抗原通透性。此外，流式细胞术（FCM）分析表明，与未修饰的 PEDV 相比，Chic-Ps 更有利于向淋巴结转运，并诱导更强的细胞和体液免疫反应。值得注意的是，Chic-Ps 诱导的鼻洗液中 PEDV 中和抗体水平高于 Chic-Ps，这一点通过蚀斑减少中和试验得到了证实。这些结果表明 Chi-C 是一种有前途的疫苗鼻腔给药系统。虽然原理验证是针对非活性 PEDV 进行的，但当需要鼻内给药时，类似的给药机制也可以应用于其他疫苗。
