Lyu J J, Yan B Y, Liu J Y, Feng Y, Wu W L, Liang X F, Cui F Q, Wang F Z, Zhang G M, Xu A Q, Zhang L
Expanded Program Immunizatin Division, Shandong Provincial Center for Disease Control and Prevention, Institute for Preventive Medicine of Shandong University, Shandong Provincial Key Laboratory of Infectious Disease Control and Prevention, Jinan 250014, China.
Zhonghua Yu Fang Yi Xue Za Zhi. 2017 Jun 6;51(6):490-495. doi: 10.3760/cma.j.issn.0253-9624.2017.06.007.
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. 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. 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 (95) 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 titer200 mU/ml. The value (95) 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 value (95) of GMC was 0.86 (0.04-1.68). 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.
评估在初次接种疫苗后低应答婴儿中,接种3剂乙肝疫苗(HepB)后4年的乙肝表面抗原抗体(抗-HBs)持久性。根据分层整群抽样,2009年8月和9月,从中国山东省济南、潍坊、烟台、威海4市的75个城镇共纳入4147名婴儿,并按照0-1-6月程序,用5μg酿酒酵母衍生乙肝疫苗(HepB-SC)进行初次接种。在第3剂初次免疫后1至6个月采集血样,采用化学发光微粒子免疫分析法(CMIA)检测抗-HBs。717名出现低应答(10 mU/ml≤抗-HBs<100 mU/ml)的婴儿接种3剂HepB。在再次接种后1个月(T(0))、4年(T(1))从总共315名婴儿中采集血样,通过CMIA检测抗-HBs、乙肝核心抗原抗体(抗-HBc)和乙肝表面抗原(HBsAg)。收集他们的出生、初次接种疫苗等信息。分别通过多因素非条件logistic回归分析和多因素线性回归模型分析,确定与抗-HBs阳性率和抗-HBs几何平均浓度(GMC)相关的危险因素。315名儿童中,男性165名(52.38%),女性150名(47.62%)。T(0)时阳性率为83.81%(264/315),T(1)时降至16.51%(149/529)。相应的GMC从473.15 mU/ml降至17.37 mU/ml。从T(0)到T(1),阳性率和GMC的年均下降率分别为33.38%和56.23%。多变量分析显示,T(0)时抗-HBs滴度较高者在T(1)时的阳性率和GMC显著更高。T(0)时抗-HBs滴度为400-<600、600-<800、800-<1000、≥1000 mU/ml者在T(1)时的阳性率显著高于抗-HBs滴度低于200 mU/ml者。阳性率的比值比(95%可信区间)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)。T(0)时抗-HBs滴度为400-<600、600-<800、800-<1000 mU/ml以及抗-HBs滴度≥1000 mU/ml者在T(1)时的GMC高于抗-HBs滴度<200 mU/ml者。GMC的β值(95%可信区间)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)。T(1)时足月儿的GMC显著高于早产儿。GMC的β值(95%可信区间)为0.86(0.04-1.68)。低应答婴儿再次接种疫苗后4年抗-HBs GMC迅速下降,但仍保持良好保护作用。再次接种疫苗后的抗-HBs持久性与再次接种疫苗后1个月的抗-HBs滴度水平相关。