应用树鼩对硫酸乙酰肝素佐剂的安全性初步评价

Safety Evaluation on Adjuvant Heparan Sulfate in Tree Shrew

目的通过检测佐剂硫酸乙酰肝素(HS)对树鼩皮肤的刺激性反应以及佐剂与甲型肝炎减毒活疫苗(Hep A-1)联合免疫树鼩后主要组织器官的病理分析,探讨以树鼩作为动物模型进行安全性评价的可行性。方法根据给药次数和皮肤是否完整将树鼩随机分组,采用树鼩同体自身左右对比的方法进行皮肤刺激性实验。根据疫苗及佐剂种类将树鼩随机分组,采用皮下免疫方式,免疫后20周取主要组织器官制备病理切片,HE染色,观察主要组织器官病理学特征。结果佐剂HS单次及多次给药对树鼩完整皮肤组和破损皮肤组的受试部位均不产生红斑、水肿等刺激性变化。与对照组相比,HepA-1免疫组以及HepA-1联合HS免疫组的心、肝、脾、肺、肾及大脑组织病理观察,均未见明显异常。结论证实了以树鼩作为动物模型进行疫苗安全性评价的可行性,为以后疫苗及药物评估平台建设提供了基础数据。

Objective To explore the feasibility of tree shrew as an animal model for safety evaluation, through the detection of adjuvant heparan sulfate （HS） of the tree shrew skin irritation and adjuvant with Hepatitis A virus attenuated live vaccine （HepA-1） combined with immune pathological analysis of main organs on tree shrews. Methods According to the dose frequency and skin integrity, the tree shrews were randomly divided into two groups, the skin irritation test performed by tree shrew own left and right contrast. According to the vaccine and adjuvant type the tree shrews randomly divided, subcutane- ous immunization. Twenty weeks after immunization, major organs are harvested to make pathological slice and perform HE staining analysis. Results The skin irritation test of adjuvant HS on tree shrews were no erythema, edema and other irritating changes of single and multiple dosing group on integrity skin or damaged skin. There is no significant pathological change between HepA-1 and HepA-1 combined with HS group on heart, liver, spleen, lung and kidney and the brain biopsy. Conclusion The experi- ment proved that the tree shrew as an animal model for vaccine safety evaluation is feasible, provide the basical data for future vaccine and drug evaluation platform.