Medical Vaccine Department, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.
Department of Biotechnology, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran.
Arch Razi Inst. 2022 Dec 31;77(6):2259-2268. doi: 10.22092/ARI.2022.360447.2583. eCollection 2022 Dec.
The nasal passage is the primary entry point for many infectious agents. Therefore, nasal vaccines that can overcome the limitations associated with antigen uptake are likely to play an important role in protecting these infectious agents. Thus, adjuvants and antigen-carrying systems that can induce a suitable mucosal and systemic immune response against their accompanying antigens are highly important. In this study, synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) accompanied by the recombinant ectodomain of influenza M2 protein were encapsulated in N-trimethyl chitosan (TMC) nanoparticles. After the preparation of TMC nanoparticles, the morphological characteristics and loading efficiency and antigen release, as well as their ability to induce efficient immune responses against M2e in intranasal inoculation in the mouse model, were studied. Based on the size and zeta potential of the nanoparticles prepared in this study, it was determined that they were all nanosized, and their positive zeta potential ranged from 25 to 28 mV, while their polydispersity index was between 0.1 to 0.2, indicating a narrow range of particle sizes. A significant increase in serum levels of the total M2e-specific IgG antibody and BALF anti-M2e IgA was observed in mice intranasally immunized with M2e/CpG-ODN/TMC as opposed to those that were intranasally immunized with M2e/TMC, M2e/CpG-ODN, free M2e, and CpG-ODN/TMC. There was also a significant change in the IgG2a/IgG1 ratio in favour of IgG2a seems that CpG-ODN is responsible for directing the immune system towards Th1. Our findings show that CpG-ODN can significantly enhance the mucosal and systemic humoral immune response against M2e when encapsulated in a suitable carrier such as TMC for intranasal administration. In conclusion, when combined with a suitable carrier, CpG-ODN can be considered an effective adjuvant for mucosal administration.
鼻腔是许多传染性病原体的主要进入点。因此，能够克服抗原摄取相关限制的鼻腔疫苗可能在保护这些传染性病原体方面发挥重要作用。因此，能够诱导针对伴随抗原的适当黏膜和全身免疫应答的佐剂和抗原载体系统非常重要。在这项研究中，含有 CpG 基序的合成寡脱氧核苷酸（CpG-ODN）与流感 M2 蛋白的重组外结构域一起包裹在 N-三甲基壳聚糖（TMC）纳米颗粒中。在制备 TMC 纳米颗粒后，研究了它们的形态特征、载药量和抗原释放，以及它们在小鼠模型中经鼻腔接种诱导针对 M2e 的有效免疫应答的能力。基于本研究中制备的纳米颗粒的大小和 zeta 电位，确定它们均为纳米级，其正 zeta 电位范围在 25 至 28 mV 之间，而其多分散指数在 0.1 至 0.2 之间，表明粒径范围较窄。与经鼻腔接种 M2e/TMC、M2e/CpG-ODN、游离 M2e 和 CpG-ODN/TMC 的小鼠相比，经鼻腔接种 M2e/CpG-ODN/TMC 的小鼠血清中总 M2e 特异性 IgG 抗体和 BALF 抗-M2e IgA 水平显著升高。IgG2a/IgG1 比值也发生了显著变化，有利于 IgG2a，这似乎表明 CpG-ODN 负责将免疫系统导向 Th1。我们的研究结果表明，当 CpG-ODN 被包裹在合适的载体（如 TMC）中用于鼻腔给药时，它可以显著增强针对 M2e 的黏膜和全身体液免疫应答。总之，当与合适的载体结合使用时，CpG-ODN 可以被认为是黏膜给药的有效佐剂。
