粘膜免疫戊型肝炎试验性疫苗的研究  

Study of an Experimental Hepatitis E Virus Vaccine for Mucosal Immunization

作　　者：周永东[1] 张明程[1] 蒋琳[2] 沈心亮[2] 毕胜利[1] 

机构地区：[1]中国疾病预防控制中心病毒病预防控制所,北京100052 [2]卫生部兰州生物制品研究所,甘肃兰州730046

出　　处：《病毒学报》2005年第1期1-5,共5页Chinese Journal of Virology

基　　金：国家高科技项目(课题编号:002AA2Z3311)资助

摘　　要：采用原核表达的戊型肝炎病毒结构区基因(HEVORF2)编码蛋白,与新型人用疫苗佐剂类MF59配制成试验性疫苗,通过粘膜免疫途径免疫实验小鼠,研究其产生粘膜免疫和体液免疫的效果。结果表明,通过滴鼻和灌胃两种粘膜免疫途径免疫BALB/c小鼠,均能诱导小鼠产生针对HEVORF2试验性疫苗的血清IgG和IgA,血清IgG的抗体滴度为1∶800～1∶1600,血清IgA抗体滴度为1∶100～1∶200。对免疫小鼠血清中IgG的动态观察表明,血清抗体可持续存在至少6个月以上。比较类MF59佐剂和传统铝盐佐剂经注射免疫所诱导产生的血清IgG抗体滴度,发现类MF59佐剂可有效增强HEVORF2重组蛋白的免疫原性4倍左右。类MF59佐剂可诱导粘膜免疫反应,在肠道粘膜部位产生SIgA,滴度为1∶100。这些结果为新型戊型肝炎病毒基因工程重组疫苗的研制提供了一条新的思路。Mucosal immune response is the first barrier against causative agents in gut tract.In order to develop a safe,efficient,convenient and economical HEV vaccine,we used recombinant HEV ORF2 antigen and novel MF59-like adjuvant to prepare a mucosal vaccine and studied its ability to elicit immune response in mice.By using this experimental HEV vaccine(namely MF59-like adjuvanted recombinant HEV ORF2 protein)to immunize BALB/c mice,we found that specific serum IgG and IgA against HEV were induced in mice through nasal dropping and stomach perfusion routes.The IgG titers in serum ranged from 1∶800 to 1∶(1 600.)The IgA titers ranged from 1∶100 to 1∶200.By mucosal administration routes,this vaccine could induce a rather long and stable (antigen)-specific serum antibody response.The IgG in serum lasted for at least 6 months.Comparing antibody titers induced by MF59-like adjuvant with that induced by alum salt adjuvant,MF59-like adjuvant could enhance the immunogenicity of HEV ORF2 protein effectively as high as 4-folds.Adjuvanted with MF59-like adjuvant,the recombinant HEV ORF2 vaccine could induce mucosal immune response,and the titer of SIgA in gut was 1∶100. This work would be useful for developing a new recombinant mucosal vaccine against HEV.

关 键 词：戊型肝炎 粘膜免疫 佐剂 试验性疫苗 体液免疫 基因工程重组疫苗 免疫保护力 

分 类 号：R512.6[医药卫生—内科学] R392.7[医药卫生—临床医学]