Key Laboratory for Molecular Animal Nutrition of Ministry of Education, Feed Science Institute, College of Animal Science, Zhejiang University (Huajiachi Campus), Qiutao North Road 164, Hangzhou 310029, China.
Mar Drugs. 2011;9(6):1038-1055. doi: 10.3390/md9061038. Epub 2011 Jun 14.
The study was conducted to investigate the promoted immune response to ovalbumin in mice by chitosan nanoparticles (CNP) and its toxicity. CNP did not cause any mortality or side effects when mice were administered subcutaneously twice with a dose of 1.5 mg at 7-day intervals. Institute of Cancer Research (ICR) mice were immunized subcutaneously with 25 μg ovalbumin (OVA) alone or with 25 μg OVA dissolved in saline containing Quil A (10 μg), chitosan (CS) (50 μg) or CNP (12.5, 50 or 200 μg) on days 1 and 15. Two weeks after the secondary immunization, serum OVA-specific antibody titers, splenocyte proliferation, natural killer (NK) cell activity, and production and mRNA expression of cytokines from splenocytes were measured. The serum OVA-specific IgG, IgG1, IgG2a, and IgG2b antibody titers and Con A-, LPS-, and OVA-induced splenocyte proliferation were significantly enhanced by CNP (P < 0.05) as compared with OVA and CS groups. CNP also significantly promoted the production of Th1 (IL-2 and IFN-γ) and Th2 (IL-10) cytokines and up-regulated the mRNA expression of IL-2, IFN-γ and IL-10 cytokines in splenocytes from the immunized mice compared with OVA and CS groups. Besides, CNP remarkably increased the killing activities of NK cells activity (P < 0.05). The results suggested that CNP had a strong potential to increase both cellular and humoral immune responses and elicited a balanced Th1/Th2 response, and that CNP may be a safe and efficacious adjuvant candidate suitable for a wide spectrum of prophylactic and therapeutic vaccines.
该研究旨在探讨壳聚糖纳米粒（CNP）对卵清蛋白（OVA）诱导的免疫反应的增强作用及其毒性。当 ICR 小鼠以 1.5mg 的剂量在 7 天间隔内两次皮下给药时，CNP 不会引起任何死亡率或副作用。ICR 小鼠在第 1 天和第 15 天，通过皮下免疫接种 25μgOVA 单独或溶解在含有 Quil A（10μg）、壳聚糖（CS）（50μg）或 CNP（12.5、50 或 200μg）的盐水中的 25μgOVA 来进行免疫接种。在二次免疫后 2 周，测量血清 OVA 特异性抗体滴度、脾细胞增殖、自然杀伤（NK）细胞活性以及脾细胞细胞因子的产生和 mRNA 表达。与 OVA 和 CS 组相比，CNP 显著增强了血清 OVA 特异性 IgG、IgG1、IgG2a 和 IgG2b 抗体滴度以及 ConA-、LPS-和 OVA 诱导的脾细胞增殖（P < 0.05）。CNP 还显著促进了 Th1（IL-2 和 IFN-γ）和 Th2（IL-10）细胞因子的产生，并上调了免疫小鼠脾细胞中 IL-2、IFN-γ 和 IL-10 细胞因子的 mRNA 表达，与 OVA 和 CS 组相比。此外，CNP 显著增加了 NK 细胞活性的杀伤活性（P < 0.05）。结果表明，CNP 具有增强细胞和体液免疫反应的强大潜力，并引发平衡的 Th1/Th2 反应，CNP 可能是一种安全有效的佐剂候选物，适用于广泛的预防性和治疗性疫苗。
