乙型肝炎疫苗初次免疫正常应答和高应答新生儿在幼儿期加强免疫对免疫保护持久性影响的配对病例对照研究

Influence of three booster doses hepatitis B vaccine on the persistence of immune-protection among infants with normal and high antibody response to primary vaccination： a matched case-control study

目的 探讨乙型肝炎（乙肝）疫苗加强免疫对初次免疫（初免）正常应答和高应答新生儿免疫持久性的影响。方法 选择乙肝疫苗初免正常应答和高应答新生儿,在其幼儿期（2-3岁）时加强免疫3剂次者作为加强免疫组,按照1：1匹配原则随机选择性别、居住乡镇相同的未加强免疫者作为未加强免疫组;于初免5年后采血检测抗-HBs和抗-HBc。结果 加强免疫组和未加强免疫组初免5年后抗-HBs阳性率分别为97.39%（224/230,95%CI：94.41%-99.04%）和53.91%（124/230,95%CI：47.24%-60.48%）,几何平均抗体浓度（GMC）分别为1140.02（95%CI：887.46-1464.46） mIU/ml和11.53（95%CI：8.73-15.23） mIU/ml;两组5年随访抗体阳性率和GMC值的差异均有统计学意义（P〈0.05）。两组HBV突破性感染率分别为0.87%（2/230）和2.17%（5/230）,差异无统计学意义（P〉0.05）。多因素分析表明,初免5年后抗-HBs阳性率与是否加强免疫和初免时抗-HBs水平独立相关,OR值分别为38.75（95%CI：16.23-92.54）和3.06（95%CI：1.51-6.17）（P值均〈0.05）。结论 乙肝疫苗初免正常应答或高应答儿童在幼儿期加强免疫可有效提高抗体持久性,但对预防HBV感染可能无明显作用。

Objective To examine the influence of three-booster-doses hepatitis B vaccines on children with normal and high antibody response to primary vaccination. Methods Antibody against hepatitis B surface antigen（anti-HBs） were detected after primary vaccination and children with normal or high response to hepatitis B primary vaccination at infancy, were identified. Children who were given three booster doses were selected to form the booster group and who were given no booster dose were 1：1 matched with the same gender and residence to form the control group. Blood samples were obtained from all the participants and tested for anti-HBs and anti-HBc, 5 years after the primary vaccination. Results The positive rates of anti-HBs response to primary vaccination were 97.39%（224/230, 95%CI：94.41%-99.04%） in the booster group and 53.91%（124/230, 95%CI：47.24%-60.48%） in the control group（P〈0.05）, 5 years after the primary vaccination. Geometric mean concentration（GMC） of anti-HBs were 1140.02（887.46-1464.46） mIU/ml in the booster group and 11.53（8.73-15.23） mIU/ml in the control group（P〈0.05）. The prevalence rates of breakthrough HBV infection were 0.87%（2/230） in the booster group and 2.17%（5/230） in the control group（P〉0.05）. Results from the multivariable analysis showed that the booster doses（OR=38.75, 95%CI：16.23-92.54） and the level of anti-HBs after the primary vaccination（OR=3.06, 95%CI：1.51-6.17） were independently associated with the positive rates of anti-HBs, 5 years after the primary vaccination（P〈0.05）. Conclusion Programs with three booster doses to children that showing normal and high antibody response to primary vaccination could improve the persistence of anti-HBs but possibly would not be able to prevent the HBV infection.