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

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

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14d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.

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.