河北省正定县监测点CHO细胞乙型肝炎疫苗接种后18-20年免疫持久性和回忆反应研究

Immune persistence and anamnestic responses 18-20 years after vaccination with Chinese hamster ovary cell derived hepatitis B vaccine in Zhengding county of Hebei province

目的评价中国仓鼠卵巢细胞乙型肝炎(乙肝)疫苗(Chinese hamster ovary cell derived hepatitis B vaccine,HepB-CHO)接种后18-20年免疫持久性和回忆反应。方法2017年10-11月在河北省正定县整群抽取1997-1999年出生且接种3剂次HepB-CHO的受试者开展问卷调查,采用化学发光法检测血清乙肝表面抗原(Hepatitis B surface antigen,HBsAg)、表面抗体(Hepatitis B surface antibody,HBsAb)和核心抗体(Hepatitis B core antibody,HBcAb),分析乙肝病毒标志物阳性率和HBsAb几何平均浓度(Geometric mean concentration,GMC);随机选择HBsAb和其他标志物均阴性的受试者,随机分为两组分别加强接种1剂次HepB-CHO和酵母细胞乙肝疫苗(Yeast cell derived HepB,HepB-Y),检测接种后30d血清HBsAb,比较抗体阳转率和GMC。结果在1352例受试者中,3剂次HepB-CHO接种后18-20年HBsAg、HBsAb和HBcAb阳性率分别为0.4%(6例)、74.5%(1007例)和1.3%(18例),HBsAb阳性者HBsAb GMC为191mIU/mL。本次调查中HBsAg阳性者在2005年、2009年和2013年调查中均为阳性;4次调查显示同一队列的受试者HepB-CHO初次免疫后6-20年HBsAg、HBcAb和HBsAb阳性率未呈显著上升或下降趋势(趋势检验:χ^(2)=3.58,P>0.05;χ^(2)=3.42,P>0.05;χ^(2)=4.54,P>0.05)。248例HBsAb阴性受试者加强1剂次HepB-CHO或HepB-Y后HBsAb总阳转率为93.1%(231例),阳转者GMC为369mIU/mL;其中HepB-CHO、HepB-Y加强免疫受试者HBsAb阳转率分别为97.7%、88.3%(χ^(2)=8.43,P<0.05),阳转者GMC分别为578mIU/mL、226mIU/mL(t=7.16,P<0.05)。结论HepB-CHO初次免疫后18-20年具有良好的免疫持久性和回忆反应,提示普通人群无必要加强免疫。

Objective To evaluate immune persistence and anamnestic responses 18-20 years after vaccination with Chinese hamster ovary cell derived hepatitis B vaccine(HepB-CHO).Methods We recruited individuals born between 1997 and 1999 who had received 3 doses of HepB-CHO in Zhengding county of Hebei province to participate in a questionnaire-base survey and study.We used chemiluminescent immunoassays to test sera for hepatitis B surface antigen(HBsAg),surface antibody(HBsAb),and core antibody(HBcAb)to determine positivity of each hepatitis B marker and geometric mean HBsAb concentrations(GMCs).We selected a random sample of subjects who were negative to HBsAb and other markers and randomized them to receive either a booster dose of HepB-CHO or a booster dose of yeast cell derived HepB(HepB-Y).We tested sera for HBsAb 30 days after vaccination to compare seroconversion rates and GMCs between the two groups.Results Among the 1352 subjects,positivity rates of HBsAg,HBsAb,and HBcAb were 0.4%(6 cases),74.5%(1007 cases),and 1.3%(18 cases),respectively,with an HBsAb GMC of 191mIU/mL in HBsAb-positive subjects.All HBsAg-positive subjects had been positive to HBsAg in studies conducted in 2005,2009,and 2013.The four studies(three previous and this study)did not show significant increases or decreases in HBsAg,HBcAb,or HBsAb positivity(trend tests:χ^(2)=3.58,P>0.05;χ^(2)=3.42,P>0.05;χ^(2)=4.54,P>0.05)among the same cohort 6-20 years after primary HepB-CHO vaccination.Among the 248 HBsAbnegative subjects,the overall HBsAb seroconversion rate was 93.1%(231 seroconversions)after a booster dose of either HepB-CHO or HepB-Y,with an overall GMC of 369 mIU/mL in seroconverting subjects.HBsAb seroconversion rates were 97.7%in the HepB-CHO booster group and 88.3%in the HepB-Y group(χ^(2)=8.43,P<0.05),with respective GMCs of 578 and 226 mIU/mL(t=7.16,P<0.05)in seroconverting subjects.Conclusions Immune persistence rates and anamnestic responses were good and stable 18-20 years after primary HepB-CHO vaccination,indicating that a booster dose is not necessary for the general population.