Objective: To estimate the immune memory at 12 years after hepatitis B vaccination and its risk factors among adults. Methods: The study was conducted in 20 villages of Qudi town in Jiyang county, Shandong province, China in 2003. Hepatitis B surface antigen (HBsAg), antibody against HBsAg (anti-HBs) and antibody against hepatitis B core antigen (anti-HBc) were tested for all healthy residents aged 15-40 years in these villages. Those who had no history of hepatitis B vaccination and were negative for all three indicators were divided into two groups randomly. Hepatitis B vaccine (HepB) was administrated to them on 0-6 month schedule or 0-1-6 month schedule respectively. Blood samples were obtained at one month after the last dose for each receipt and were quantitatively detected for anti-HBs. Finally a total of 629 participants completed HepB vaccination and anti-HBs testing, including 288 of two-dose group and 341 of three-dose group respectively. In 2015, an additional dose of HepB (challenge dose) was administrated to those who were negative for anti-HBs at follow-up (anti-HBs <10 mIU/ml) to evaluate the immune memory. A total of 93 blood samples, including 50 of two-dose group and 43 of three-dose group respectively, were drawn at 14 days after the challenge dose and anti-HBs was quantitatively detected. The anti-HBs geometric mean concentrations (GMCs) after the challenge dose were compared between the two groups. Multivariate linear regression model was built to find the independent risk factors associated with immune memory response (anti-HBs GMC after the challenge dose). Results: The challenge dose of HepB and post-challenge anti-HBs detection were completed among 93 participants. Totally 92 (98.92%, 92/93) participants were found holding immune memory (anti-HBs after the challenge dose was ≥10 mIU/ml). The immune memory positive rates were 100% (50/50) and 97.67% (42/43) in the two-dose group and three-dose group respectively and the corresponding anti-HBs GMC after challenge dose were 2 684.30 (95%CI: 1 721.71-4 185.08) mIU/ml and 3 527.48 (95%CI: 2 145.15-5 800.58) mIU/ml (P=0.410). The anti-HBs GMC after the challenge dose were 1 908.33 (95%CI: 1 190.01-3 060.27) mIU/ml, 4 004.20 (95%CI: 2 257.90-7 101.12) mIU/ml and 8 682.16 (95%CI: 5 813.94-12 965.36) mIU/ml among the participants whose anti-HBs titer was<4, 4-6 and 7-9 mIU/ml at follow-up, respectively (P=0.002). There was no correlation between immune schedule and anti-HBs GMC after the challenge dose; β (95%CI) was -0.07 (-0.34-0.20), P=0.601. Conclusion: The immune memory after primary hepatitis B vaccination lasted for at least 12 years among adults. The immune memory response was independently associated with ant-HBs titer at follow-up, but might be similar between 0-6 month schedule and 0-1-6 month schedule.
目的： 分析成人接种乙型肝炎疫苗（HepB）12年后的免疫记忆持久性及其相关因素。 方法： 于2003年，以山东省济阳县曲堤镇的20个村为研究场所，选取15~40岁健康居民中既往无HepB免疫史且HBsAg、抗-HBs和抗-HBc三项全阴者，按照0、6个月（2剂次组）和0、1、6个月（3剂次组）免疫程序接种HepB，接种后1个月采集血标本，定量检测抗-HBs，共629名，每组分别为288和341名；于2015年，对上述对象中抗-HBs浓度<10 mIU/ml者接种1剂次HepB（激发剂次），于接种后14 d采集血标本，定量检测抗-HBs，共93名，每组分别为50和43名。比较不同组接种激发剂次后抗-HBs几何平均浓度（GMC）水平差异，并采用多因素线性回归模型分析免疫程序与接种激发剂次后抗-HBs GMC的相关性。 结果： 93名接种激发剂次者中，92名出现免疫记忆阳性（激发剂次后抗-HBs浓度>10 mIU/ml），阳性率为98.92%。2剂次组和3剂次组免疫记忆阳性率分别为100%（50例）和97.67%（42例），接种激发剂次后抗-HBs GMC分别为2 684.30（95%CI：1 721.71~4 185.08）和3 527.48（95%CI：2 145.15~5 800.58）mIU/ml（P=0.410）；随访时抗-HBs浓度<4，4~6和7~9 mIU/ml者接种激发剂次后抗-HBs GMC分别为1 908.33（95%CI：1 190.01~3 060.27）、4 004.20（95%CI：2 257.90~7 101.12）和8 682.16（95%CI：5 813.94~12 965.36）mIU/ml（P=0.002）。免疫程序与激发剂次后抗-HBs浓度无相关性，β（95%CI）值为-0.07（-0.34~0.20），P=0.601。 结论： 成人接种HepB后免疫记忆至少可持续12年；随访抗体水平与免疫记忆抗体水平独立相关，未发现HepB免疫程序与免疫记忆抗体水平有关。.
Keywords: Adult; Hepatitis B vaccine; Immune memory; Immune persistence.