卵清蛋白模型疫苗/壳聚糖纳米粒鼻腔递送的研究

 目的研究壳聚糖纳米粒作为蛋白类疫苗的新载体,并评价其鼻腔给药后所产生的免疫效果。方法使用离子胶凝法来制备亲水性壳聚糖纳米粒,选用卵清蛋白(OVA)为模型蛋白,考察其粒径、表面电位和蛋白包封率。并比较不同剂型鼻腔免疫BALB/c小鼠后产生的不同免疫效果。结果壳聚糖载药纳米粒最佳粒径大约360nm,表面电位为+40mV,卵清蛋白的包封率可达到80%～90%。OVA/壳聚糖纳米粒鼻腔给药后能诱导更高更长期的体液免疫反应(IgG水平),和肌注高剂量卵清蛋白溶液产生的免疫效果相当;并且能诱导比可溶性抗原显著提高的黏膜免疫反应(IgA水平)。结论壳聚糖纳米粒制备方法温和,对蛋白等具有较高的包封率,鼻腔给药后能诱导较强的免疫反应,因此有望成为蛋白类疫苗鼻腔给药的新载体。

Studies on Protein Antigen/Chitosan Nanoparticles for Nasal Vaccine Delivery

OBJECTIVE To prepare Chitosan nanoparticles(NPs) as new carriers for vaccine delivery and to evaluate the effect of this system on the immune response for intranasal delivery.METHODS Ovalbumin(OVA),used as a model antigen,was entrapped within chitosan nanoparticles by an ionotropic gelation technique.OVA- entrapped nanoparticles were characterized for their size, electrical charge, entrapment efficiency.Different formulations were then administered intranasally to conscious mice in order to evaluate their immune responses.RESULTS The nanoparticles with optimum diameter of 360 nm exhibited a positive electrical charge (+40 mV) and associated OVA quite efficiently (entrapment efficiency: 80%~90%).Following intranasal administration, OVA-entrapped nanoparticles elicited an increasing and long-lasting systemic immune response (IgG levels) and also, this response was similar to the results of high dose intramuscular administration.Moreover, the mucosal response (IgA levels) of nanoparticles was significantly higher than that obtained from soluble antigen.CONCLUSION Chitosan nanoparticles prepared by mild preparation methods show high OVA entrapment efficiency.When being administered intranasally, NP can induce high immune response in mice.These findings suggest that chitosan nanoparticles are promising carriers for nasal vaccine delivery.