【作者】 毛群颖； 郭增兵； 姚昕； 李秀玲； 王一平； 刘刚； 梁争论； 李凤祥； 王军志；

【Author】 MAO Qunying1,GUO Zengbing2,YAO Xin1,LI Xiuling3,WANG Yiping1,LIU Gang1,LIANG Zhenglun1,LI Fengxiang1,WANG Junzhi1 (1.National Institute for the Control of Pharmaceutical and Biological Products,Beijing 100050; 2.Hualan Biological Engineering Inc,Henan 453003; 3. National Vaccine and Serum Institute,Beijing 100024)

【机构】 中国药品生物制品检定所； 华兰生物工程股份有限公司； 北京生物制品研究所；

【摘要】 目的:比较我国不同企业研发的肠道病毒71型(EV71)疫苗原液和成品疫苗的免疫原性,为疫苗临床试验提供依据。方法:应用来源于3家疫苗研发企业的EV71疫苗原液(B1、B2、B3),以及相应原液制备的3批成品疫苗(临床申报剂量:V1、V2、V3;相同抗原含量:V1-1、V2-1、V3-1),分别采取2针程序免疫小鼠,检测免疫1针和2针后血清中和抗体效价。结果:3批不同毒株、不同工艺制备的疫苗原液免疫原性相近,免疫剂量均为430U/0.5ml/只时,1针后中和抗体阳性率为83.3-90.0%,2针均为100%,中和抗体效价分别为1:34.9-1:45.9和1:139.4-1:285.7;与AL(OH)3吸附后,3批成品疫苗的免疫原性均出现明显增强,162U/0.5ml/只的剂量即均可得到与430U/0.5ml/只原液相近的抗体阳转率和效价,2针免疫后V3-1抗体效价显著高于V1-1和V2-1(1:357.3,1:111.3和1:97.9,P分别为0.004和0.001)。当3批疫苗均采用临床申报剂量免疫时(162、521、548U/0.5ml/只),1针免疫后中和抗体阳性率(80-100%)和抗体效价(1:46.8-1:115.4)均无显著性差异(P值均>0.05),2针后中和抗体阳性率均为100%,V3批抗体效价显著高于V1批(1:958.2、1:316.8,P为0.017)。结论:3家企业EV71原液的免疫原性接近,成品疫苗2针免疫后均可诱导高效价中和抗体产生,但不同企业的中和抗体升高水平呈现差别,提示临床试验中需比较不同疫苗加免后的免疫原性。更多还原

【Abstract】 Objective:To compared the immunogenicity of vaccine stock solutions and final vaccines of enterovirus 71(EV71), which were researched and developed by three different enterprises of China, and provide bases for the further clinical trails of EV71 vaccines. Methods:The immunization schedule consisted of two inoculations in mice separately using three bulks of EV71 purified antigen(B1、B2、B3)from three enterprises and three bulks of EV71 finial lot vaccines (Clinical declaring dose:V1、V2、V3;Equal antigenic concentration:V1-1、V2-1、 V3-1)made of the corresponding EV71 aqueous bulk mentioned above. And the neutralizing antibody titer of sera were tested after the first inoculation and the second inoculation, respectively. Results Three bulk vaccine stock solutions from different strains and preparations showed the close immunogenicity. When immunizing dose was 430U/0.5ml/each mouse, the positive rate of neutralizing antibody was 83.3-90.0% after the 1st inoculation and 100% after the 2nd inoculation, with Geometric Mean Titers (GMTs) of neutralizing antibody was 1:34.9-1:45.9 and 1:139.4-1:285.7, respectively. Moreover, the immunogenicity of three bulk finished vaccines after adsorbed with AL(OH)3 was all significantly increased, in result the positive rate of neutralizing antibody of finished vaccines (162U/0.5ml/each mouse) was close to that of vaccine stock solutions (430U/0.5ml/each mouse). After two immunizations, GMTs of V3-1 was significantly higher than that of V1-1 and V2-1(1:357.3,1:111.3,1:97.9; P=0.004 and 0.001). When clinical declaring doses (162、521、548U/0.5ml/each mouse ) were employed for three vaccine products, there existed no significant difference between the positive rates of neutralizing antibody (80-100%)and between antibody GMT(s1:46.8-1:115.4)after the 1st inoculation (P>0.05), and the positive rates of neutralizing antibody were all 100% after the 2nd inoculation. In addition, antibody GMTs of V3 was significantly higher than that of V1 (1:958.2, 1:316.8; P=0.017). Conclusion:The immunogenicity of EV71 vaccine aqueous bulk solutions from three different enterprises were close to each other and high-titers neutralizing antibody was induced after two inoculations. However, significantly difference in increased levels of neutralizing antibody among different enterprises was observed, which suggests that the comparison of immunogenicity should be focused on in clinical trails after boost dose.更多还原