乙型肝炎疫苗初次免疫正常应答和高应答婴儿初次免疫5年后免疫记忆持久性随访观察

目的 探讨乙型肝炎(乙肝)疫苗初次免疫(初免)正常应答和高应答新生儿在初免后5年免疫记忆情况及其影响因素。方法 对初免正常应答和高应答新生儿于初免后5年检测其抗-HBs,其中低于保护水平(10 mIU/ml)者接种1剂次乙肝疫苗(激发剂次)并于接种后14 d采集血标本,再次检测抗-HBs,并计算激发剂次后抗-HBs阳转率(≥10 mIU/ml)和GMT。将检测的初免抗体、随访抗体和激发剂次后抗体均从低到高分成不同等级,分析激发剂次后抗体的影响因素。结果 37.98%(980/2 580)初免正常应答和高应答新生儿在初免后5年抗-HBs已降至保护水平以下,其中激发剂次后98.95%(757/765)出现抗体阳转,GMT为2 811.69(95%CI:2 513.55～3 145.19) mIU/ml。激发剂次后抗体滴度随初免抗体水平和随访抗体水平的升高而升高(F值分别为5.46、10.23,均P<0.000 1)。多因素分析显示,激发剂次后抗体滴度与性别、出生体重、早产等无关(P>0.05),而与初免抗体和随访抗体水平独立相关(OR=1.001,95%CI:1.000～1.002,P<0.001;OR=1.28,95%CI:1.81～1.39,P<0.001)。结论 新生儿乙肝疫苗初免后5年存在较强的免疫记忆;免疫记忆的强度与初免抗体及激发剂次前抗体水平有关。

Persistence of immune memory to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination: a five-year following-up study

Objective To examine the immune memory status to hepatitis B vaccine among infants with normal or high antibody response to primary vaccination, 5 years after the primary vaccination and the risk factors associated with the immune memory. Methods Titers of the antibody against hepatitis B surface antigen (anti-HBs) were detected, five years after the primary vaccination among children who appeared normal or high response to hepatitis B primary vaccination in infancy. Those whose anti-HBs titers were low than protective level (10 mIU/ml) were given a challenge dose of hepatitis B vaccine and titers of anti-HBs were detected 14 days after the challenge. Positive rate and geometric mean titer (GMT) of anti-HBs were calculated. Level of the anti-HBs titers after primary vaccination,at following-up and after the challenge periods were divided into different levels, respectively. Risk factors associated with the levels of anti-HBs titer after the challenge were examined by univariate analysis that and multivariable analysis. Results Anti-HBs waned to the level below protective standard among 37.98% of the children with normal or high antibody response to hepatitis B primary vaccination; among those children whose anti-HBs were below the protection standard. The seroconversion rate and GMT of anti-HBs after the challenge dose were 98.95%(757/765) and 2 811.69 mIU/ml 95% Confidence Interval(CI):2 513.55-3 145.19 mIU/ml], respectively. Titers and levels of anti-HBs after the challenge, appeared an increase with anti-HBs after primary vaccination and the anti-HBs in the following-up (F=5.46,10.23 respectively; P<0.000 1 for both) periods. Results from the multivariable analysis showed that gender, premature birth and birth weight were factors insignificantly associated with the anti-HBs titers after the dose of challenge, while the anti-HBs levels were independently associated with the levels of anti-HBs titer after the challenge OR=1.001(95%CI:1.000-1.002),P<0.001;OR=1.28(95%CI:1.81-1.39),P<0.001] at the following-up periods. Conclusions Strong immune memory could be found among those children with normal or high responses to hepatitis B vaccination, 5 years after the primary vaccination. The intensity of immune memory might be associated with the anti-HBs titer after primary vaccination as well as the anti-HBs titers before the challenge dose was given.