重组中国仓鼠卵巢细胞乙型肝炎疫苗应用于成人后细胞及体液免疫的效果研究

Study on the cellular and humoral immunity effect of recombinant Chinese hamster ovary cell hepatitis B vaccine in adults

目的 通过随机双盲对照试验的方法,评价10μg和20 μg重组中国仓鼠卵巢（CHO）细胞乙型肝炎（简称乙肝）疫苗应用于成人后细胞免疫及体液免疫的效果.方法 选择18～45岁未接种过乙肝疫苗、乙肝五项指标均为阴性的642名成人作为研究对象,按照随机数字表法分为两组,每组321名,以0、1、6个月的接种程序分别接种10μg和20μg重组CHO乙肝疫苗.每个研究对象在接种第2针1个月后采血,以雅培化学发光的方法（I2000）检测乙肝表面抗体（anti-HBs）滴度值,以评价体液免疫反应.利用Excel随机函数的方法选择其中153名研究对象采血分离淋巴细胞,以酶联免疫斑点法（ELISPOT）检测体外刺激后淋巴细胞所产生的细胞因子白细胞介素4（IL-4）、γ干扰素（IFN-γ）的斑点数（SFC）,以评价细胞免疫反应.结果 10μg和20μg两个剂量组anti-HBs阳转率分别为88.8%（285/321）和95.3%（306/321）,95%可信区间分别为：85.4%～92.2%和93.0%～97.6%（x2=9.39,P＜0.01）.20μg组IL-4免疫斑点数（-x）=20.31）高于10μg组（（-x）=8.19,t=3.27,P＜0.01）,并且随着anti-HBs水平升高,两组IL-4斑点水平也明显升高,anti-HBs水平与IL-4间呈现正相关（Spearman秩相关系数=0.538,P＜0.0001）;IFN-γ斑点数在两组中差异无统计学意义（10μg组：（-x）=1.49;20μg组：（-x）=0.86;t=1.83,P＞0.05）.结论 20μg重组CHO乙肝疫苗体液免疫及细胞免疫效果均优于10μg重组CHO乙肝疫苗,成人乙肝免疫预防应优先选择20μg重组CHO乙肝疫苗.

Objective To evaluate the cellular and humoral immunity effect of 10 μg and 20 μgrecombinant Chinese hamster ovary （CHO）cell hepatitis B vaccine in adults by randomized double-blind controlled trials. Method A total of 642 adults aged 18 -45 years old,non-vaccinated against hepatitis B,and hepatitis B five blood indicators negative were selected as the study subjects. The study subjects were randomly divided into two groups and each group had 321 subjects. The subjects were given 10 μg and 20 μg recombinant CHO hepatitis B vaccination respectively by O, 1st, 6th month schedule. Blood sample was collected from each study subject one month after the second dose vaccination. The anti-HBs level was detected by Abbott chemiluminescence detection method （ I2000 ） to evaluate humoral immunity status. Of all the study objects,153 cases were randomly selected by the Excel random function. Their blood samples were collected and Lymphocyte were separated to detect the IL-4 and IFN-γ levels in vitro by enzyme-linked immunospot （ELISPOT） method to evaluate the cellular immunity status. Results The anti-HBs seroconversion rates in 10 μg and 20 μg dose group were 88. 8% （ 285/321 ） and 95. 3% （ 306/321 ）respectively, and 95% CI were 85.4% - 92. 2% and 93.0% - 97.6% respectively. The spot forming cell （ SFC ） of IL-4 of the 20 μg-dose group （ （-x） = 20. 31 ） were significantly higher than the 10 μg-dose group （（-x） =8. 19, t = 3.27, P ＜ 0. 01 ） . With the increasing of anti-HBs titer, the SFC of IL-4 also went up significantly. There was a positive correlation between SFC of IL-4 and anti-HBs （Spearman correlation coefficient =0. 538 ,P ＜0. 0001 ）. No significant difference was found for IFN-γSFC in two groups（ 10 μg group：（-x） = 1.49;20 μg group：（-x） = 0.86;t= 1.83,P＞ 0.05）. Conclusion The humoral and cellular immune effects of 20 μg recombinant CHO hepatitis B vaccine are better than that of the 10 μg recombinant CHO hepatitis B vaccine. 20 μg recombinant CHO hepatitis B vaccine should be chosen as the adult＇s hepatitis B prevention vaccine.