Pharmaceutical Development of Green Innovations Group (PDGIG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
Thai Traditional Medicine College, Rajamangala University of Technology Thanyaburi, Pathum Thani 12130, Thailand.
Int J Biol Macromol. 2021 Jul 31;183:1096-1105. doi: 10.1016/j.ijbiomac.2021.05.050. Epub 2021 May 8.
Intranasal (IN) administration, a non-invasive route, is explored to overcome the limitations of conventional subcutaneous (SC) injection for Japanese encephalitis (JE) immunisation. Mucoadhesive nanoparticles (NPs) are recognised for the benefits they offer via IN delivery, such as extended retention time of the vaccine on the mucosa. The purpose of this study was to evaluate immunisation effect of live attenuated Japanese encephalitis-chimeric virus vaccine (JE-CV)-loaded mucoadhesive NPs based on chitosan (CS) or chitosan maleimide (CM), a novel mucoadhesive polymer, via the IN route to improve the mucosal immunisation against JE. The results revealed that IN immunisation stimulated seroprotection following PRNT evaluation. Moreover, compared with SC immunisation, IN immunisation in mice provided a higher sIgA level, leading to improved mucosal immune response. In addition, chitosan-based NPs showed an adjuvant effect on the IN vaccine due to their mucoadhesive and antigen-uptaken properties. CM NPs successfully induced sIgA. In contrast, SC JE-CV immunisation induced negligible mucosal immunity. These immunological advantages revealed that JE-CV-loaded mucoadhesive NPs are a promising approach for IN vaccination as an alternative route for JE protection due to the stimulatory effects on both mucosal and systemic immune responses.
鼻腔（IN）给药是一种非侵入性途径，旨在克服传统皮下（SC）注射在日本脑炎（JE）免疫中的局限性。黏膜黏附纳米颗粒（NPs）因其通过 IN 给药带来的益处而得到认可，例如延长疫苗在黏膜上的滞留时间。本研究旨在评估基于壳聚糖（CS）或壳聚糖马来酰亚胺（CM）的载有活减毒日本脑炎嵌合病毒疫苗（JE-CV）的黏膜黏附纳米颗粒（NPs）通过 IN 途径进行免疫接种的效果，以改善针对 JE 的黏膜免疫。结果表明，PRNT 评估显示，IN 免疫接种可刺激血清保护。此外，与 SC 免疫接种相比，IN 免疫接种在小鼠中提供了更高的 sIgA 水平，从而改善了黏膜免疫反应。此外，基于壳聚糖的 NPs 由于其黏膜黏附性和抗原摄取特性，对 IN 疫苗具有佐剂作用。CM NPs 成功诱导了 sIgA。相比之下，SC JE-CV 免疫接种几乎不能诱导黏膜免疫。这些免疫学优势表明，载有 JE-CV 的黏膜黏附纳米颗粒是 IN 疫苗接种的一种有前途的方法，可作为 JE 保护的替代途径，因为它对黏膜和全身免疫反应都具有刺激作用。
