Objective: Assess the 4-year antibody against hepatitis B surface antigen (anti-HBs) persistence after revaccination with 3-dose of hepatitis B vaccine (HepB) among low-responder infants following primary vaccination. Methods: According to stratified cluster sampling, a total of 4 147 infants were enrolled and primarily vaccinated with 5 μg HepB derived in Saccharomyces Cerevisiae (HepB-SC) at 0-1-6 months schedule from 75 towns of Jinan, Weifang, Yantai, Weihai prefectures, Shandong Province, China in Aug and Sep 2009. Blood samples were collected one to six months after the third dose of primary immunization and tested for anti-HBs using chemiluminescence microparticle immunoassay (CMIA). 717 infants who appeared low response (10 mU/ml ≤ anti-HBs<100 mU/ml) were revaccinated with 3-dose of HepB. Blood samples were collected from a total of 315 infants one month (T(0)), four years (T(1)) after revaccination and anti-HBs, antibody against hepatitis B core antigen (anti-HBc) and hepatitis B surface antigen (HBsAg) were detected by CMIA. Information about their birth, primary vaccination were collected. The risk factors associated with positive rate of anti-HBs and GMC of anti-HBs were identified by multiple non-conditional logistic regression analysis and multifactor linear regression model analysis, respectively. Results: Among 315 children, 165 (52.38%) were male and 150 (47.62%) were female. The positive rate was 83.81% (264/315) at T(0) and it decreased to 16.51% (149/529) at T(1). The corresponding GMC decreased from 473.15 mU/ml to 17.37 mU/ml. The average annual decreasing rate of positive rate and GMC was 33.38% and 56.23% from T(0) to T(1). Multivariable analysis showed the positive rate and GMC among those whose anti-HBs titer higher at T(0) were significantly higher at T(1). The positive rate at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000, ≥1 000 mU/ml at T(0) were significantly higher than those whose anti-HBs titer less than 200 mU/ml. The OR (95%CI) of the positive rate was 4.29 (1.03-17.84), 4.53 (1.25-16.47), 4.19 (1.10-15.97) and 9.13 (2.91-28.63), respectively. The GMC at T(1) among those whose anti-HBs titer 400-<600, 600-<800, 800-<1 000 mU/ml and those whose anti-HBs titer ≥1 000 mU/ml at T(0) were higher than those whose anti-HBs titer<200 mU/ml. The b value (95% CI) of GMC was 0.84 (0.06-1.62), 1.13 (0.46-1.79), 1.33 (0.65-2.01) and 1.88 (1.33-2.44), respectively. GMC among full-term infants were significantly higher than premature infants at T(1). The b value (95% CI) of GMC was 0.86 (0.04-1.68). Conclusion: Anti-HBs GMC decreased rapidly 4 years after revaccination among low-responder infants, but still kept good protection. The anti-HBs persistence after revaccination was associated with anti-HBs level of titer one month after revaccination.
目的： 分析乙型肝炎疫苗（HepB）基础免疫低应答婴儿再次免疫后4年时抗体持久性。 方法： 于2009年8—9月，以山东省济南、潍坊、烟台、威海4个市为研究现场，按照分层整群抽样方法共抽取75个乡镇，以抽取的乡镇中所有按照"0-1-6"程序初次接种5 μg重组酿酒酵母HepB的4 147名婴儿为入组对象。第3剂次后1~6个月时采集静脉血2 ml，经化学发光微粒子免疫分析法（CMIA）检测抗-HBs为10~<100 mU/ml者共717名，即低应答者。按照"0-1-6"程序为低应答者再次接种3剂次HepB（共494名），并于再次免疫后1个月、4年时（分别简称为T(0)和T(1)时）采血，采用CMIA法检测抗-HBs、抗-HBc和HBsAg，同时收集其基本情况及基础免疫等信息，共随访了315名。分别采用多因素非条件logistic回归模型和多因素线性回归模型分析T(1)时抗-HBs阳性和几何平均浓度（GMC）的影响因素。 结果： 315名随访对象中，男性占52.4%（165名），女性占47.6%（150名）。T(0)时抗-HBs阳性率（抗-HBs≥100 mU/ml者所占的比例）为83.8%（264/315），T(1)时降为16.5%（149/529），抗-HBs阳性率年递减率为33.38%；T(0)时抗-HBs的GMC为473.15 mU/ml，T(1)时降为17.37 mU/ml，年递减率为56.23%。多因素分析显示，与T(0)时抗-HBs<200 mU/ml者相比，T(0)时抗-HBs在400~<600、600~<800、800~<1 000、≥1000 mU/ml者T(1)时抗体阳性率较高，OR（95%CI）值分别为4.29（1.03~17.84）、4.53（1.25~16.47）、4.19（1.10~15.97）和9.13（2.91~28.63）。与T(0)时抗-HBs<200 mU/ml者相比，抗-HBs在400~<600、600~<800、800~<1 000、≥1000 mU/ml者T(1)时抗-HBs的GMC较高，b（95%CI）值分别为0.84（0.06~1.62）、1.13（0.46~1.79）、1.33（0.65~2.01）和1.88（1.33~2.44）;足月婴儿较早产婴儿T(1)时抗-HBs的GMC更高，b（95% CI）值为0.86（0.04~1.68）。 结论： HepB基础免疫低应答婴儿T(1)时抗-HBs的GMC仍保持在保护水平以上；低应答婴儿再次免疫后抗体持久性主要与再次免疫的抗体水平相关。.
Keywords: Hepatitis B antibodies; Hepatitis B vaccines; Infant; Low-responders.