细胞免疫和遗传因素对乙型肝炎疫苗阻断母婴传播效果的影响  

Thee influence of cellular immunity and genetic factor on the effect of mother to infant transmission interrupted with hepatitis B vaccine

作　　者：廖雪雁[1] 梁争论[1] 李艳萍 李荣成 刘建源[3] 吴小音[1] 张瑞[1] 方鑫[1] 农艺 黄月奎 张华远[1] 李河民[1] 

机构地区：[1]中国药品生物制品检定所,北京100050 [2]广西壮族自治区疾病控制中心 [3]北京生物制品研究所

出　　处：《中华微生物学和免疫学杂志》2006年第12期1070-1075,共6页Chinese Journal of Microbiology and Immunology

基　　金：国家"十五"攻关项目课题基金支持(编号:2004BA718B02)

摘　　要：目的比较接种重组乙肝疫苗后不同体液免疫应答高危儿童的细胞免疫反应特点,进一步探讨母婴阻断失败、无应答的机理。方法124名母亲HBsAg和HBeAg双阳性的新生儿按常规乙肝的免疫程序接种重组CHO和酵母乙肝疫苗,于第1针免后3、7、12月检测HBsAg和抗-HBs,判定免疫成功或失败的新生儿,首针后60～120月(平均80月)再次检测HBsAg和抗-HBs指标,选取8名免疫重组乙肝疫苗母婴阻断失败儿童、4名免后无应答抗体反应的儿童和11名母婴阻断成功的儿童采集静脉血样,分离淋巴细胞,应用ELISPOT方法检测产生IL-2斑点形成细胞的数量,并对斑点数和表面抗体滴度的相关性进行比较,同时分析HLA-A、-B、DRB1和DQB1等位基因的多态性。结果(1)124名研究对象中有77．4％的儿童可产生保护性表面抗体,成功阻断母婴传播;13．7％的人免疫失败,感染乙肝;8．9％的儿童则对乙肝疫苗呈无应答状态。(2)免疫成功组产生IL-2细胞数(55．2±42．22)显著高于免疫失败组(3,75±3．24)和抗体无应答组(6．75±3．59),P<0．01。(3)儿童免疫乙肝疫苗后的表面抗体滴度与经乙肝疫苗诱导产生的特异性分泌IL-2的T细胞数量呈显著性正相关(r =0．601,P<0．01)。(4)HLA-B*48在对酵母乙肝疫苗无应答的儿童中占有25％的频率,显著高于免疫成功(2．2％)和失败的儿童(0％),P<0．05。对CHO疫苗无应答儿童的HLA-DRB1*15的频率显著高于免疫成功和失败的儿童(P<0．05)。结论乙肝疫苗母婴阻断失败和免后抗体无应答儿童的细胞免疫应答显著低于阻断成功的儿童,并且可能与遗传因素有关。Objective To inveatigate the characteristicsof cellular immune response smong individuals differentially responsive to recombinant hepatitis B vaccine, whose mothers were infectod with hepatitis B virus. Further objective is to evaluate the mechanism of mother to infant transmission interrupted with hepatitis B vaccine. New born infants （n = 124）, whose mother were positive for HBsAg and HBeAg, were vaccinated with normal 3 doses of recombinant hepatitis B vaccine. HBsAg and anti-HBs were detected 3, 7, 12 and 60-120 months after vaccination. Furthermore, after 60-120 months , separate peripheral blood mononuclear cells （PBMC） from unsuccessfully responsive individuals （ n = 8）, non-responsive individuals （ n = 4） and responsive individuals for hepatitis B vaccine （n= 11） respectively. T cell number secreting IL-2 was determined by ELISPOT method and analysis of the correlation between anti-FIBs and the number of T cell secreting IL-2. HLA-A, -B, DRB1 and DQB1 loci were tested. Results （1） Among 124 children, 77.4% can elicit protective anti-HBs titers and interrupt the transmission from mother to infant succeasfully , however, 13.7% failed to the vaccine and developed hepatitis B infection. Others were either non- or hypo-responsive to the vaccine. （2） The spot forming number of TH 1 secreting IL-2 of the responsive individuals was 55.2 ± 42.22, which was significantly higher than these of the unsucceasful and non-responsive individuals （P 〈 0.01）. （3） The anti-HBs peak titer was relative to the cell number secreting IL-2 stimulated with HBsAg. （4） In the group of recombinant yeast hepatitis B vaccine, HLA-B 48 was correlated with non-responsive individuals to the vaccine, however, HLA-DRB1 ＊ 15 in the non-responsive individuals to recombinant CHO hepatitis B vaccine was more frequent than that in responsive individuals and unsuccessful responsiveness to the vaccine （P 〈 0.05）. Conclusion The cellular immune response of the unsuccessf

关 键 词：重组乙型肝炎疫苗 母要传播 HLA 细胞免疫 ELISPOT 

分 类 号：R392[医药卫生—免疫学]