初步探索以“动物法则”评价鼠疫组分疫苗的临床有效性  

Primary research on determination of clinical efficacy for plague component vaccine with animal rule

作　　者：焦磊[1] 吴智远[1] 常娅莉[1] 辛有全[2] 孟繁岳[3] 王婷[1] 卜培英[1] 张青雯[2] 祁芝珍[2] 王秉翔[1] 

机构地区：[1]兰州生物制品研究所有限责任公司第七研究室甘肃省疫苗工程技术研究中心,甘肃兰州730046 [2]青海省地方病预防控制所青海省鼠疫防控及研究重点实验室,青海西宁811602 [3]江苏省疾病预防控制中心,江苏南京210009

出　　处：《微生物学免疫学进展》2016年第6期5-10,共6页Progress In Microbiology and Immunology

基　　金：科技重大专项(2013ZX09402302-217;2014ZX09-102047-002)

摘　　要：目的依据＂动物法则＂,探索被动免疫小鼠对鼠疫强毒菌攻击的有效性,为间接评价鼠疫组分疫苗临床有效性提供依据。方法以小鼠为观察对象,依据小鼠耐受正常人血清剂量和小鼠体内异源动物血清代谢动力学研究,确定小鼠耐受正常人血清剂量和攻击时间,基于此对小鼠进行鼠疫组分疫苗免疫人血清被动免疫,观察小鼠抵抗鼠疫强毒菌攻击的存活率和存活时间,判定小鼠被动保护鼠疫强毒菌攻击的有效性。结果 BALB/c小鼠对正常人血清耐受量为1.0 m L,3~4 h间抗体滴度最高。小鼠抵抗鼠疫强毒菌攻击试验显示,在14 d的观察期内,经2MLD、6 MLD和10 MLD鼠疫强毒菌攻击的被动免疫小鼠,存活率分别为57%、25%和42%,平均存活时间依次为11.2 d、8.7 d和9.8 d;1 MLD攻击非免对照小鼠全部死亡,平均存活时间5.3 d。结论初步证实利用被动免疫小鼠可间接评价鼠疫组分疫苗临床有效性的可行性。Objective On the basis of ＂animal rule＂,the efficacy for a passive immunized mouse was studied in a challenge experiment to evaluate plague component vaccine,indirectly,and provide a scientific support. Methods Based on the tolerance dose of normal human serum in a tested mouse and pharmacokinetic analysis of heterologous serum in a mouse vivo,the determination of tolerance dose and survival time for the tested mouse to normal human serum were conducted after passive immunization,and moreover,the survival rate and mean survival time were observed to decide the mouse efficacy from a passive protection by using of immunized serum of human anti-plague component vaccine. Results A total of 1m L of normal human serum was determined as a tolerance dose for a BALB / c mouse,and the highest antibody titer was in 3-4 hrs after immunization. In a challenge process with 14 days,it was by using of immunized serum of human anti plague vaccine component vaccine,then challenged with 2 MLD,6 MLD and 10 MLD virulent plaque strain,the mouse survival rate reached 57%,25% and 42%,and mean time to death prolonged to 11.2,8.7 and 11.2 days,respectively,in comparison of no survival and 5.3 days mean time to death for the control mouse. Conclusion The primary study confirmed that the evaluation of clinical efficacy for plague component vaccine was feasible by using a passive immunized mouse in the challenge experiment.

关 键 词：鼠疫组分疫苗 动物法则 被动保护 疫苗有效性 

分 类 号：R392-33[医药卫生—免疫学]