无细胞耻垢分枝杆菌疫苗对豚鼠的长期毒性研究

Evaluation of long-term toxicity for Mycobacterium smegmatis vaccine in guinea pigs

目的:观察无细胞耻垢分枝杆菌疫苗对豚鼠的长期毒性。方法:48只豚鼠随机均分成无细胞耻垢分技杆菌疫苗低、中、高剂量组(疫苗用量分别为50,250和500μg·kg-1)和阴性对照组,每周1次,连续7周肌内注射疫苗,阴性对照组给予等体积的生理氯化钠溶液。在实验前、中、末期(n=12)和恢复期(n=4)观察动物体重、白蛋白和球蛋白比值、抗疫苗抗体IgG和总IgE的含量;在实验末期和恢复期对豚鼠作病理组织学检查和骨髓细胞学检查。结果:阴性对照组豚鼠抗疫苗抗体IgG始终为阴性,疫苗组豚鼠注射疫苗后抗疫苗抗体IgG阳转;各组豚鼠在整个实验过程中体重稳定增加,白蛋白和球蛋白比值未见明显改变,血清IgE均为阴性;各脏器未见病理性损害和免疫复合物沉积,各脏器系数与阴性对照组比较未见统计学差异;骨髓各系造血细胞未见抑制现象。结论:无细胞耻垢分枝杆菌疫苗对豚鼠无长期毒性。

Objective：To assess the long-term immunotoxicology for Myeobacterium smegmatis vaccine in guinea pigs. Methods： 48 guinea pigs were randomized to intramuscularly inject low, middle or higher dose of Mycobacterium smegmatis vaccine （50,250 and 500μg·kg^-1） or normal saline alone as control once a week for 7 weeks. The effect was assessed based on the changes of body weight, ratio of albumin to globin, IgG against vaccine, and total IgE pre, during, at the end and post dosing. The histopathological and marrow cytological examinations of the guinea pigs were performed at the end of the dosing and in the recovery period. Results： The guinea pigs as control had negative IgG at all. The guinea pigs administering the three doses of vaccine turned the positive IgG and negative total IgE after immunization and had normal weight gain. The ratios of albumin to globin showed no significant changes. No histological lesions and immunological complex deposits were observed. No statistical difference of organ coefficient was found between control group and vaccine groups. No repression for hematopoietic cells in the marrow occurred. Conclusion： The Mycobacterium smegmatis vaccine has no long-term toxicity in guinea pigs.