人用狂犬病疫苗暴露前免疫程序在实验动物中的比较

Comparison of immunization strategies for human rabies pre-exposure prophylaxis in laboratory animals

目的比较我国现行狂犬病疫苗暴露前免疫程序(0-7-21或28)与WHO新推荐的免疫程序(0-7)在安全性、有效性及保护性方面的差别,为修订《狂犬病预防控制技术指南》相关内容提供实验动物方面的数据支持。方法按照我国现行的3针法、WHO新推荐的2针法等狂犬病暴露前免疫程序,将小鼠随机分成5组,即0-7-21组(3针组)、0-7组(2针组)、0-14组、0-21组和对照组。观察小鼠生存状态,每间隔5 d称重,比较不同免疫程序的安全性。首次免疫后7、14、21、28和35 d采血,检测抗狂犬病病毒中和抗体(rabies virus neutralizing antibodies,RVNA),确认其有效性。免疫后35 d以致死剂量的CVS-11狂犬病病毒对各组小鼠攻毒,评价不同免疫程序的保护性。结果接种疫苗后,各组小鼠体重增长差异无统计学意义。免疫后14 d,各免疫组小鼠RVNA阳转率均为100%,可对小鼠提供完全保护作用。0-7-21 d组和0-7 d组免疫后35 d RVNA水平差异有统计学意义(P<0.05),其余各时间点差异均无统计学意义(P>0.05)。2针免疫程序组中,除0-7组与0-21组在免疫后21 d、35 d的RVNA水平差异有统计学意义外(P<0.05),其余各组各时间点的RVNA水平差异均无统计学意义(P>0.05)。在保护性试验中,各免疫组小鼠生存率均为100%。结论我国现行的3针法狂犬病疫苗暴露前免疫程序(0-7-21)与WHO新推荐的2针法免疫程序(0-7)在动物实验中具有相似的有效性和保护性,鉴于2针法免疫程序在节约成本的同时具有更好的依从性,建议相关部门尽快开展临床试验以推进该方案的实施。

Objective To compare the differences in the safety,efficacy and protective effects of rabies vaccine using the current pre-exposure prophylaxis schedule in China(0-7-21 or 28)and the newly recommended immunization program of WHO(0-7),aiming to provide data support for modifying the related content of Technical Guideline for Human Rabies Prevention and Control.Methods The mice were randomly divided into five groups,namely 0-7-21 group(3-injection regimen),0-7 group(2-injection regimen),0-14 group,0-21 group and control group,according to the current 3-injection regimen(0-7-21)in China and the 2-injection regimen(0-7)recommended by WHO.The survival status of the mice was observed.The mice were weighed every five days to compare the safety of different immunization procedures.Rabies virus neutralizing antibodies(RVNA)were detected 7,14,21,28 and 35 d after the initial immunization.On day 35,the mice in each group were challenged with lethal dose of CVS-11 rabies virus to evaluate the protective effects of different pre-exposure immunization procedures.Results There was no significant difference in weight gain of mice after vaccination.The positive rate of RVNA was 100%in all immunized groups from day 14,which could provide complete protection to mice.There was a significant difference in RVNA levels between 0-7-21 and 0-7 groups at 35 d(P<0.05),but there was no statistical difference at other time points(P>0.05).RVNA level had a significant difference between 0-7 and 0-21 groups at 21 d and 35 d(P<0.05).There was no statistical difference in RVNA level between other groups at each time point(P>0.05).In the protective test,the survival rates of mice in all immune groups were 100%.Conclusions The current 3-injection pre-exposure immunization procedure for rabies vaccine(0-7-21)and the newly recommended 2-injection immunization procedure(0-7)had similar efficacy and protective effects in animal tests.In view of the cost saving and better compliance of the 2-injection immunization procedure,it was recommended that relevant departments should conduct clinical trials as soon as possible to promote the implementation of this program.