小鼠品系对狂犬病疫苗效价检测的影响

Effect of different strains of mice immunized with rabies vaccine on detection of titer

目的探讨小鼠品系(KM和ICR小鼠)对狂犬病疫苗效价检测的影响。方法将狂犬病疫苗及人用狂犬病疫苗效力检定国家标准品(简称国家标准品)用PBS按1∶25、1∶125、1∶625、1∶3125稀释,分别经腹腔免疫KM和ICR小鼠(雌雄各半),每个品系小鼠每个稀释度免疫16只,0.5 m L/只,间隔1周加强免疫1次,免疫剂量及途径同上。分别于初次免疫后0、7、14 d对各组小鼠进行称重;初次免疫后14 d,用狂犬病病毒(rabies virus,RABV)攻击毒株CVS2(5~100 LD_(50)),经脑腔攻毒,0.03 m L/只,统计攻毒5 d后发生死亡和呈典型狂犬病脑症状的小鼠数量,根据获得的国家标准品ED_(50),采用Reed-Muench法计算狂犬病疫苗相对效力。结果两个品系的小鼠在免疫阶段体质量均呈上升趋势,KM比ICR小鼠体质量增长更快。采用KM小鼠检测国家标准品的lgED_(50)均在期望范围(2.10~2.75)内,而ICR小鼠的lgED_(50)则高于其范围。采用KM小鼠检测狂犬病疫苗的效价均显著低于ICR小鼠(t=2.887~6.619,P均<0.05)。结论小鼠品系可显著影响狂犬病疫苗效价的检测结果,针对不同品系小鼠应采用不同标准,以确保疫苗检测结果的准确性。

Objective To study the effect of different strains of mice(KM and ICR)immunized with rabies vaccine on thedetection of titer.Methods The rabies vaccine and the national standard for the efficacy verification of rabies vaccine forhuman use(referred to as national standard)were diluted with PBS at the ratios of 1∶25,1∶125,1∶625 and 1∶3125,and KM and ICR mice with half male and half female were immunized intraperitoneally respectively.Sixteen mice of each strain wereimmunized with 0.5 m L/mouse at each dilution.The immunization was strengthened once every one week at the same dose androute.The mice in each group were weighed 0,7 and 14 d after the initial immunization.After 14 d of the initial immunization,the mice were subjected to intracranial attack with rabies virus(RABV)CVS2(5-100 LD_(50)),0.03 m L/mouse.The numberof mice with death and typical rabies brain symptoms 5 d after the attack was counted.According to the national standard ED_(50),the relative efficacy was calculated by Reed-Muench method.Results The body mass of the two strains of miceshowed an increasing trend during the immunization stage,and the body mass of KM mice increased faster than that of ICRmice.The lgED_(50)values of the national standard in KM mice were all within the expected range of 2.10-2.75,while thevalues in ICR mice were higher than the range.The titers of rabies vaccine in KM mice were all significantly lower than thosein ICR mice(t=2.887-6.619,each P<0.05).Conclusion Mouse strains can significantly affect the results of rabies vaccine titer determination,and different standards should be adopted for different strains of mice to ensure the accuracy of vaccine detection results.