目的 对商业化规模生产场地变更前后的口服六价重配轮状病毒减毒活疫苗（Vero细胞）进行单次给药毒性和重复给药毒性实验，以考察非临床安全性的可比性。方法 分别采用商业化规模生产场地变更前后的轮状病毒减毒活疫苗（Vero细胞），对SD大鼠以6 mL/只的剂量（临床拟用剂量为2.0 mL）经口灌胃给药，评价疫苗急性毒性。分别以2 和6 mL/只的剂量于第1、15、29、43天重复灌胃给药4次（恢复期4周），评价疫苗长期毒性。结果 单次给药毒性实验中，生产场地变更前后的疫苗最大耐受量均为6 mL/只，按体重折算，为人拟用剂量的50~200倍；变更前后疫苗组的动物第0—14天体重增长和日进食量均值均与同期对照组相近，分别为每只33~44 g（雌）、109~123 g（雄）和18~20 g（雌）、25~29 g（雄）。重复给药毒性实验中，未观察到不良反应的剂量水平为6 mL/只，低、高剂量组变更前后疫苗的动物体重、日进食量均值和体温的变化趋势均与同期对照组相似；实验动物的血液与生化指标也均未见与生产场地变更相关的异常改变。在同等给药剂量下，各疫苗卫星组血清IgG抗体的阳转率差异（P值为0.474~1.000）和几何平均滴度差异（t值为0.05~0.85，P值为0.442~0.965）均不具有统计学意义，且变化趋势一致；变更前低、高剂量疫苗卫星组血清IgG抗体阳转率和几何平均滴度（1∶lgx）最高水平分别为80.0%、80%和1.61、1.81，变更后分别为90.0%、100.0%和1.79、1.91；实验动物脏器及组织病理学切片均未见与生产场地变更相关的异常改变。结论 商业化规模生产场地变更前后的口服六价重配轮状病毒减毒活疫苗（Vero细胞）在SD大鼠体内均显示出良好的安全性，二者的单次给药毒性和重复给药毒性均具有可比性。

Objective To evaluate the non-clinical safety comparability of Reassortant Rotavirus Vaccine, Live, Oral, Hexavalent (Vero Cell) produced in pilot and commercial facilities by assessments of single- and repeated-dose toxicity.Methods SD rats were administered by gavage with vaccines produced in pilot and commercial facilities, respectively, at 6 mL dosage, while the proposed clinical dosage was 2.0 mL. The long-term toxicity of the vaccine was assessed through 4 repeated intragastric administrations at doses of 2 or 6 mL per rat on day 1, 15, 29, and 43, with a 4-week recovery period. Results In the single-dose toxicity test, maximum tolerated dose was 6 mL per rat for vaccines produced in both facilities, which was 50-200 times the intended human dose converted by body weight. The body weight gain from day 0—14 and mean daily food intake of rats that received vaccines produced in pilot and commercial facilities were simliar to control groups， which were 33-44 g and 18-20 g, respectively, for female rats and 109-123 g and 25-29 g, respectively, for male rats. In the repeated-dose toxicity test, the no-observed-adverse-effect level was 6 mL per rat. The trends of body weight, mean daily food intake and body temperature in low- and high-dose groups with vaccines produced in pilot and commercial facilities were all simliar to control groups. The blood and biochemical indicators of animals did not show abnormal changes related to different facilities.In equivalent dose vaccine satellite groups, there were no statistically significant differences in seroconversion rate (P=0.474-1.000) and geometric mean titer (GMT) (t=0.05-0.85,P=0.442-0.965) of serum IgG antibodies against rotavirus, and the change trend was consistent. The peak of IgG antibody seroconversion rates and GMTs (1∶lgx) in low- and high-dose vaccine (produced in pilots facilities) satellite groups were 80.0%, 80.0% and 1.61,1.81, while the corresponding vaccine （produced in commercial facilities） satellite groups were 90.0%,100.0% and 1.79,1.91,respectively. The organs and histopathological sections of animals did not show abnormal changes related to different facilities.Conclusion Reassortant Rotavirus Vaccines, Live, Oral, Hexavalent (Vero Cell) produced in pilot and commercial facilities both show good safety in SD rats and are comparable in single-and repeated-dose toxicity studies.