目的 通过对变更稳定剂的乙型脑炎减毒活疫苗进行SD大鼠长期毒性试验，评价疫苗的非临床安全性。方法 分别向160只SD大鼠皮下注射3次变更稳定剂前后的乙型脑炎减毒活疫苗或氯化钠注射液（阴性对照），对动物进行临床观察，体重、食量、血细胞计数、血液生化、体温、临床病理、T淋巴细胞亚群和特异性IgG抗体的检测及尿液分析、眼科检查。结果 实验期间，动物未见明显与给药相关的异常反应。虽然部分疫苗组别与阴性对照组相比，体重增长、食量、血细胞计数、血液生化指标差异均有统计学意义（t=2.03~4.26，P =0.011~0.042），但未见与稳定剂变更相关的异常改变，体温、凝血功能、T淋巴细胞亚群未见具有统计学意义的改变（t=1.35~1.98，P =0.052~0.186）。至恢复期结束时，所有疫苗组的所有动物仍可检测到抗体，各抗体效价未见明显降低。末次给药后3 d和恢复期结束时，阴性对照组及所有疫苗组安乐死动物的大体观察、组织病理学检查均未见明显异常改变。变更前后疫苗的毒性反应、局部刺激性和免疫原性未见明显不同。结论 变更稳定剂后的乙型脑炎减毒活疫苗的大鼠长期毒性试验结果符合动物安全性评价要求。

Objective To evaluate the non-clinical safety of live attenuated Japanese encephalitis vaccine with changed stabilizer by long term toxicity test in SD rats.Methods A total of 160 SD rats were subcutaneously injected with Japanese encephalitis vaccine with changed or unchanged stabilizer or NaCl(negative control) for 3 times. Animals were clinically observed, monitored for body weight, food intake, blood cell count, blood biochemistry, urinalysis, body temperature, clinical pathology, T lymphocyte subsets, and specific IgG antibody as well as performed urinalysis and ophthalmic examination.Results During the test, no significant abnormal reactions related to administration was observed. The body weight gain, food intake, blood cell count, and blood biochemistry showed statistically significant differences between certain vaccine groups and negative control （t=2.03-4.26，P=0.011-0.042），but no abnormal changes related to the stabilizer change were seen. There were no statistically significant changes in body temperature, coagulation function,and T lymphocyte subsets (t=1.35-1.98，P =0.052-0.186). By the end of recovery period, antibodies were detected in all animals in all vaccination groups, and there was no significant decrease in antibody titers. At 3 days after the last dose of administration and at the end of recovery period, no significant abnormal change was observed in the gross anatomy and histopathological examination of euthanized animals in all vaccination groups and negative control groups. There was no significant difference in toxicity, local irritation, and immunogenicity between vaccine groups with changed or unchanged stabilizer.Conclusion The long-term toxicity test results of live attenuated Japanese encephalitis vaccine with changed stabilizer in rats meet the requirements of animal safety evaluation.