大肠杆菌重组颗粒性戊型肝炎疫苗对恒河猴的免疫保护  

Protective Efficacy of a Particulate Recombinant(E.coli)Hepatitis E Vaccine on Rhesus Monkey

作　　者：张军[1] 李益民 李少伟[1] 欧山海[1] 黄果勇 何志强[1] 葛胜祥[1] 鲜阳凌 逄淑强 夏宁邵[1] 

机构地区：[1]厦门大学细胞生物学与肿瘤细胞工程教育部重点实验室,厦门361005 [2]北京万泰生物药业有限公司,北京102200 [3]广西壮族自治区疾病控制中心,广西南宁430021

出　　处：《病毒学报》2004年第1期1-6,共6页Chinese Journal of Virology

基　　金：福建省科技重大项目 ( 2 0 0 2F0 13 ) ;教育部跨世纪人才优秀培养计划

摘　　要：大肠杆菌表达的戊型肝炎病毒 (HEV)衣壳蛋白ORF2片段HEV 2 39重组蛋白颗粒 ,经铝佐剂吸附后 ,分别以5 μg、1 0 μg和 2 0 μg剂量免疫恒河猴 ,2 8天时以相同剂量加强免疫 1次 ,3周后分别以不同病毒滴度的基因Ⅰ型或基因Ⅳ型HEV静脉攻击。结果 ,加强后 3周 ,3个免疫剂量组猴的抗体几何平均滴度分别为 1∶2 71 75、1∶344 0 9、1∶4 16 0 7,以世界卫生组织参比血清定量 ,则分别为 1 0 98IU/ml,1 35 7IU/ml、1 72 4IU/ml。每个剂量免疫组及对照组各有 3只猴接受 1 0 7病毒滴度基因Ⅰ型HEV感染 ,对照组 3只猴均被成功感染 ,2只出现肝炎 ;2 0 μg免疫组 3只猴均未被感染 ;1 0 μg和 5 μg免疫组各有 2只猴未被感染 ,另 1只猴出现短暂感染 ,免疫猴均未出现肝炎。 3个剂量免疫组及对照组另外 3只猴 ,接受 1 0 4病毒滴度基因Ⅰ型HEV感染 ,对照组 3只猴均被感染 ,1只出现肝炎 ;而免疫猴均未被感染 ,也未出现肝炎。 3只 1 0 μg免疫猴和 3只对照猴分别接受 1 0 7病毒滴度基因Ⅳ型HEV感染 ,对照组均被感染并出现肝炎 ,而免疫组均未出现肝炎 ,有 2只未被感染 ,另 1只被短暂感染。另有 3只 1 0 μg免疫猴和 3只对照猴分别接受 1 0 4病毒滴度基因Ⅳ型HEV感染 ,对照组均被感染 ,而免疫组均未被感染。这些结果表明An E.coli expressed recombinant protein HEV 239,which was derived from capsid protein ORF2 of hepatitis E virus(HEV)and aggregated into virus like particle,was adsorbed with alum adjuvant,then immunized rhesus monkeys with 5μg,10μg,or 20μg dosages.Three weeks after the animals were boosted on day 28,different virus dosages of a HEV genotype Ⅰ strain and a HEV genotype Ⅳ strain were used to challenge the monkeys as well as the control monkeys intravenously. The results showed that the geometry mean titer of anti HEV of three vaccine dosage groups were 1∶27*!175,1∶34*!409 and 1∶41*!607 respectively.The anti HEV quantity calculated by ELISA using a WHO reference serum were 1*!098 IU/ml,1*!357 IU/ml and 1*!724 IU/ml respectively.Three monkeys of each vaccinated groups and control group were challenged with 10 7 virus titer of HEV genotype Ⅰ strain.While all three monkeys of control group were infected by the virus and two suffered from hepatitis,all three monkeys of 20μg vaccinated group,two of 10μg vaccinated group and two of 5μg vaccinated group were protected from infection,and moreover all vaccinated monkeys were protected against hepatitis.Another three monkeys of each vaccinated group and control group were challenged with 10 4 virus titer of HEV genotype Ⅰ strain. While all three monkeys of the control group were infected and one suffered from hepatitis,all the vaccinated monkeys were protected from infection as well as hepatitis.Three monkeys vaccinated with 10μg vaccine and three control monkeys when challenged with 10 7 virus titer of HEV genotype Ⅳ strain,all three monkeys of the control group were infected and suffered from hepatitis,and the vaccinated monkeys all were protected from hepatitis and two were protected from

关 键 词：戊型肝炎 疫苗 原核表达 恒河猴 保护率 

分 类 号：R512.6[医药卫生—内科学]