4种国产甲型肝炎疫苗接种后2年免疫效果研究

Comparison of four different domestic hepatitis A vaccines: two years follow-up study of a randomized controlled clinical trial in China

目的评价甲型肝炎（甲肝）灭活疫苗（HepA-I）和甲肝减毒活疫苗（HepA-L）接种后2年的免疫效果。方法 924名1.5~6岁儿童随机双盲分配到5组,分别接种2针科兴HepA-I、1针科兴HepA-I、1针普康HepA-L、1针昆明所HepA-L、1针长春所HepA-L。接种疫苗后第12和24个月时采血检测甲肝抗体,剔除免前阳性和未采血者,比较各组不同时间点系列血清抗体几何平均浓度（geometric mean concentration,GMC）和阳性率。结果第12个月时,5组甲肝抗体（抗-HAV）IgG阳性率分别为96.6%（28/29）、89.3%（25/28）、96.0%（24/25）、95.7%（22/23）、95.2%（20/21）,各组间差异无统计学意义;5组抗-HAV IgG GMC分别为1261.5、82.5、138.8、236.9和176.4mIU/ml,各组间差异有统计学意义（P〈0.01）。其中2针HepA-I组的抗-HAV IgG GMC（1 261.5 mIU/ml）高于1针HepA-I组（82.5mIU/ml）和HepA-L组（178.4mIU/ml）（P〈0.01）。1针HepA-I组抗-HAV GMC（82.5mIU/ml）低于1针昆明所组（236.9mIU/ml）（P〈0.01）。其他1针组的组间差异无统计学意义。第24个月时,5组抗-HAV IgG阳性率分别为100.0%（29/29）、85.7%（24/28）、96.0%（24/25）、95.7%（22/23）和100.0%（21/21）,各组间差异无统计学意义;5组抗-HAV GMC分别为662.6、85.2、147.5、140.6和266.8mIU/ml,各组间差异有统计学意义（P〈0.01）。其中2针HepA-I组的抗-HAV GMC（662.6mIU/ml）高于1针HepA-I组（85.2mIU/ml）和HepA-L组（173.8mIU/ml）（P〈0.01）。1针HepA-I组的抗-HAV IgG GMC（85.2mIU/ml）低于1针长春所组（266.8mIU/ml）（P〈0.01）。其他1针组的组间差异无统计学意义。结论接种后2年,4种国产甲肝疫苗免疫效果均较好,2针HepA-I组抗-HAV GMC显著高于1针HepA-I组和HepA-L组,1针HepA-I组免疫效果与HepA-L组基本一致。

Objective To evaluate the immunogenicity among an inactivated hepatitis A vaccine （HepA-D and three kinds of live attenuated vaccines （HepA-L） that were used for the Expanded Plan Immunization in Chi- na. Methods A randomized, controlled, and double-blind clinical trial was conducted among healthy children aged 1.5-6 years. A total of 924 subjects were randomly divided into 5 groups. Two groups were immunized with either one dose （group A1） or two-doses （group A2） of HepA-I. The other three groups were vaccinated with one dose of HepA-L from three different manufactures （groups B, C and D） . Serum samples were col- lected at 12 and 24 months after vaccination for the evaluation of immune responses. This study focused on the 12 and 24 months serial serum results. Results The geometric mean concentration （GMC） of anti-HAV IgG in group A2 was significantly higher than that in groups A1, B, C and D at 12-month （1261.5 vs 82.5,138.8, 236.9 and 176.4 mlU/ml, respectively, P〈0.01） . The GMC level at A1 group was significantly lower than that in group C （82.5 vs 236.9 mlU/ml, P〈0.01） . There were no significant differences of GMC levels among other groups. At 24-month, the GMC in group A2 was still significantly higher than that in groups A1, B, C and D （662.6 vs 85.2, 147.5, 140.6, 266.8 mIU/ml, P〈0.01） .The GMC level in group A1 was significantly lower comparing to group D （85.2 vs 266.8 mIU/ml, P〈0.01） . However, at 12 month and 24-month, no significant differences were observed in the seroconversion rates among these five groups. Conclusions The best immune response was induced bytwo dose HepA-I.