5μg和10μg重组乙型肝炎疫苗初次免疫正常应答和高应答新生儿5年抗体持久性比较

Comparison of antibody persistence after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine among newborns with normal and high response：a five-year following-up

目的 比较5 μg和10 μg乙型肝炎疫苗（HepB）初次免疫（初免）正常应答和高应答新生儿初免后5年的抗体持久性。方法 选用5 μg（重组啤酒酵母）和10 μg（重组汉逊酵母）HepB，按照＂0-1-6＂程序完成3剂次初免的新生儿，并在接种第3剂次后1~6个月（T0）和5年（T1）后分别采集静脉血，采用化学发光微粒子免疫分析法（CMIA）定量检测抗-HBs，比较两剂量接种后正常应答和高应答（T0时抗-HBs ≥ 100 mIU/ml）者T1时的抗体阳性率（抗-HBs ≥ 10 mIU/ml）和平均抗体浓度（GMC）；通过多因素分析探讨接种剂量与抗体持久性的关系。结果 HepB 5 μg组和10 μg组分别共有1 883名和1 495名观察对象纳入分析，T1时抗-HBs阳性率分别为49.92%（943/1 883）和75.92%（1 135/1 495），差异有统计学意义（χ2=237.75，P〈0.001）；GMC分别为10.23（95%CI：9.38~11.16）mIU/ml和28.91（95%CI：26.65~31.35）mIU/ml，差异有统计学意义（F=280.36，P〈0.001）。10 μg组T1时抗-HBs阴转者抗-HBs滴度分布与5 μg组的差异有统计学意义（χ2=39.75，P〈0.001）。多因素分析显示，排除其他因素影响后，HepB初免剂量与T1时抗-HBs阳性率和抗-HBs滴度均独立相关[P〈0.001，OR=1.44（95%CI：1.20~1.73）；P〈0.001，β=0.27（95%CI：0.14~0.40）]。结论 新生儿使用10 μg重组HepB初免后5年抗-HBs持久性优于5 μg重组HepB。

Objective To compare the antibody persistence 5 years after primary immunization with 5 μg and 10 μg recombinant hepatitis B vaccine （HepB） among newborns with normal and high response. Methods Newborns who completed three doses of 5 μg HepB made by recombinant dexyribonucleic acid technique in Saccharomyces （HepB-SC） or 10 μg HepB made by recombinant dexyribonucleic acid technique in Hansenula polymorpha （HepB-HP） were recruited. Standardized questionnaire was used and blood samples were collected 1-6 months （T0） and five years （T1） after the third dose respectively. The titer of anti-HBs was detected by chemiluminescence microparticle imunoassay （CMIA）. Those who achieved normal or high antibody response （anti-HBs titer ≥ 100 mIU/ml） were included in the study and the positive rate （≥ 10 mIU/ml） and titer of anti-HBs at T1 were compared between 5 μg HepB group and 10 μg HepB group. Multivariable analysis was conducted to identify the independent factors associated with the antibody persistence. Results The positive rate of anti-HBs at T1 was 49.92% （943/1 883） and 75.92% （1 135/1 495） respectively in 5 μg HepB group and 10μg HepB group, the difference was significant （χ2=237.75, P〈0.001）. The anti-HBs geometric mean concentrations at T1 were 10.23 mIU/ml （95%CI：9.38-11.16） and 28.91 mIU/ml （95%CI：26.65-31.35） in the two groups respectively, the difference was also significant （F=280.36, P〈0.001）. Among those whose anti-HBs titer was 〈10 mIU/ml at T1, the distributions of anti-HBs titer were significantly different between 5 μg HepB group and 10 μg HepB group （χ2=39.75, P〈0.001）. The multivariable analysis showed that dosage of HepB was independently associated with both positive rate and titer of anti-HBs at T1 after excluding the other factors[P〈0.001, OR=1.44 （95%CI：1.20-1.73）; P〈0.001, β=0.27 （95%CI：0.14-0.40）]. Conclusion Five year anti-HBs persistence after primary immunization with 10 μg HepB might be better than that after primary immunization with 5 μg HepB among infants who achieved normal or high anti-HBs response after primary HepB immunization.