Department of Medical Parasitology and Mycology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Department of Clinical Immunology, Faculty of Medicine, Ilam University of Medical Sciences, Ilam, Iran.
Int J Biol Macromol. 2022 May 31;208:962-972. doi: 10.1016/j.ijbiomac.2022.03.146. Epub 2022 Mar 26.
This study was aimed to encapsulate and construct the Toxoplasma gondii surface antigen (SAG1) and naltrexone hydrochloride (NLT-HCL) as an adjuvant within chitosan nanoparticles (CS-NPs) to develop efficacious vaccine against T. gondii. Seven groups of BALB/c mice were immunized with SAG1, chitosan (CS), NLT-SAG1, CS-SAG1, CS-SAG1-NLT, CS-NLT and PBS. The efficiency of each approach was detected in vivo mouse immunization. Moreover, the immuno-induction effect of SAG1 recombinant protein and CS-NPs-based NLT-HCL as an adjuvant in a vaccine delivery was evaluated. Experimentally, Th1/Th17 biased cellular and humoral immune responses were activated in the mice immunized with CS-SAG1-NLT nanoparticles that were accompanied by considerable increased production of IFN-γ, IL-17, IL-12, IL-4, IFN-γ/IL-4 ratio, IgG, IgG2a. This group of mice also showed significantly increased survival time post-challenging. The successful encapsulated SAG1 recombinant protein and NLT-HCL, as an adjuvant, within CS-NPs can induce immune responses against toxoplasmosis. We could incorporate NLT-HCL adjuvant into the CS-NPs based delivery systems, which makes CS-NPs attractive as a colloidal carrier system for NLT-HCL as secondary adjuvant. This new approach or the simultaneous use of CS and NLT demonstrated that the co-administration of CS-NPs and NLT-HCL induce production of IL-17 cytokine. This approach can be used for vaccination purposes, in which Th17 and Th1 cellular immune are considered the key of the successful immune response.
本研究旨在将刚地弓形虫表面抗原(SAG1)和盐酸纳曲酮(NLT-HCL)包封并构建为壳聚糖纳米粒子(CS-NPs)中的佐剂,以开发针对刚地弓形虫的有效疫苗。用 SAG1、壳聚糖(CS)、NLT-SAG1、CS-SAG1、CS-SAG1-NLT、CS-NLT 和 PBS 免疫七组 BALB/c 小鼠。体内小鼠免疫检测每种方法的效率。此外,还评估了 SAG1 重组蛋白和基于 CS-NPs 的 NLT-HCL 作为佐剂在疫苗传递中的免疫诱导作用。实验中,用 CS-SAG1-NLT 纳米粒子免疫的小鼠激活了 Th1/Th17 偏向的细胞和体液免疫反应,伴随着 IFN-γ、IL-17、IL-12、IL-4、IFN-γ/IL-4 比值、IgG、IgG2a 的产生显著增加。该组小鼠的存活时间也显著延长。成功地将 SAG1 重组蛋白和 NLT-HCL 作为佐剂包封在 CS-NPs 中,可以诱导针对弓形虫病的免疫反应。我们可以将 NLT-HCL 佐剂纳入基于 CS-NPs 的递送系统中,这使得 CS-NPs 成为 NLT-HCL 作为二级佐剂的有吸引力的胶体载体系统。这种新方法或 CS 和 NLT 的同时使用表明,CS-NPs 和 NLT-HCL 的共同给药可诱导 IL-17 细胞因子的产生。该方法可用于疫苗接种,其中 Th17 和 Th1 细胞免疫被认为是成功免疫反应的关键。