不同剂量配比的实验性甲型肝炎戊型肝炎联合疫苗的免疫原性研究  

Immunogenicity of experimentally combined hepatitis A and hepatitis E vaccine at different dosage ratio

作　　者：董晨[1] 戴星[2] 孟继鸿[1] 

机构地区：[1]东南大学医学院病原生物学与免疫学系,江苏南京210009 [2]东南大学医学院附属中大医院皮肤科,江苏南京210009

出　　处：《细胞与分子免疫学杂志》2007年第2期130-133,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金资助项目(30271231);江苏省科技发展计划高技术研究基金资助项目(BG2006607);教育部留学回国人员科研启动基金资助项目(2004-176)

摘　　要：目的研究实验性甲型肝炎(甲肝)戊型肝炎(戊肝)联合疫苗的免疫原性,探讨两种抗原组分间的相互作用。方法制备9种不同剂量配比的实验性甲戊肝联合疫苗,与单价疫苗对照一起免疫15组(共120只)小鼠,定时采血,以ELISA和中和试验检测抗HAV和抗HEV的抗体。结果高剂量的HAV抗原(5×105U/L)与不同剂量的HEV抗原(200、100、50mg/L)配制的联合疫苗,诱导的抗HAV中和抗体的滴度可达1∶1024,含25×104、125×103U/LHAV抗原的联合疫苗诱导的中和抗体滴度为1∶512,不同剂量的HEV抗原对抗HAV中和抗体的产生均无明显影响。与单价戊肝疫苗相比较,联合疫苗诱导的抗HEV抗体水平均有明显升高,且随联合疫苗中HAV抗原的含量(5×105、25×104、125×103U/L)的增加而升高,HEV抗原的剂量在一定范围内(200、100、50mg/L)与抗HEV抗体产生无明显关系。采用基于逆转录套式PCR的中和试验表明,各联合疫苗组的免疫血清均可中和HEV。结论实验性甲、戊肝联合疫苗内HAV抗原对HEV抗原的免疫原性具有增强作用,而HEV抗原对HAV抗原的免疫原性无明显影响。AIM： To evaluate the immunogenicity of ex- perimentally combined hepatitis A and hepatitis E （cHA ＋ E） vaccine and analyze the interactions between the two antigenic components in vaccine. METHODS： Nine different dosage ratio of the cHA ＋ E vaccine, A500 ＋ E200, A500 ＋ E100, A500 ＋ E50, A250 ＋ E200, A250 ＋ E100, A250 ＋ E50, A125 ＋ E200, A125 ＋ E100 and A125 ＋ E50 （ U ＋ mg ）/L, was prepared from an inactivated hepatitis A （HA） vaccine and a hepatitis E （HE） vaccine. 120 mice were immunized with the cHA ＋ E vaccine, HA vaccine and HE vaccine alone in different doses, respectively. Mice were bled before immunization and 2, 4, 6, 8, 10, 12 and 14 weeks post immunization. Specific antibodies against hepatitis A and E viruses were detected by ELISA and neutralization assay. RESULTS. After immunization with different dosages of cHA ＋ E vaccine, all animals developed hepatitis A virus antibody （anti-HAV） and hepatitis E virus antibody （antiHEV）. Anti-HAV responses increased with the concentration of the HA vaccine component in the cHA ＋ E vaccine. Anti-HAV neutralizing antibody titers reached 1： 1 024 when mice were immunized with cHA ＋ E vaccine prepared from higher dosage （500 U/mL） of the HA vaccine. The titers only reached 1：512 when lower dosages （250 and 125 U/mL） of HA vaccine were applied. However, different dosages （200, 100 and 50 mg/L） of the HE vaccine component in the cHA ＋ E vaccine developed no effects on the production of anti-HAV neutralizing antibody. In addition, comparing with the single HE vaccine, the cHA ＋ E vaccine induced higher level of anti-HEV response. The anti-HEV level increased with the concentration of HA vaccine component in the cHA ＋ E vaccine. However, there was no obvious relationship between the anti-HEV levels and the different dosages （200, 100 and 50 mg/L）of the HE vaccine component in the cHA ＋ E vaccine. Immune sera elicited by the cHA ＋ E vaccine neutralized HEV infectivity when detected

关 键 词：甲型肝炎病毒 戊型肝炎病毒 联合疫苗 剂量配比 免疫原性 

分 类 号：R373.21[医药卫生—病原生物学] R512.6[医药卫生—基础医学]