【摘要】 目的了解乙肝疫苗免疫失败者的HBV S基因的变异情况。方法采用流行病学、ELISA与分子生物学方法,筛选乙肝疫苗免疫失败者。采用聚合酶链反应(PCR)、基因克隆和测序的方法,对乙肝疫苗免疫失败者的HBVS基因进行分析,并与HBV参考序列S基因进行比较,分析其变异情况。结果从2 564份受检者中,筛选出2例(0.78‰)HBsAg(-)/HBeAg(+)/HBcAb(+)乙肝疫苗免疫失败者(HBs1、HBs2),经HBV DNA荧光定量PCR检测和HBV S基因PCR扩增,结果均为阳性,为B基因型。其S基因序列与参考序列(JX429908.1)相比,同源性为98.57%,且乙肝疫苗免疫失败者S基因在第363位和第467位分别由野生型的C变为A、G变为A,HBsAg 121位和156位氨基酸C和W缺失。结论乙肝疫苗免疫失败者HBV S基因上第363位和第467位碱基存在错义突变(C→A和G→A),改变了HBsAg的结构和抗原性。更多还原

【Abstract】 Objective To evaluate the correlation between hepatitis B vaccine failure and S gene mutation.Methods Field epidemiological investigation,ELISA and Molecular biological methods were used to evaluate the hepatitis B vaccine efficacy.Polymerase chain reaction(PCR),gene cloning and nucleotide sequencing were done to analyze the hepatitis B virus S gene.Results Two cases with an infrequent pattern of HBV serological markers [HBsAg(-) / HBeAg(+) / HBcAb(+)](0.78‰) were found in 2 564 research subjects.HBV S gene of the hepatitis B vaccine failures were positively identified by PCR,which shared 98.57% sequence homology with HBV S gene from wild type HBV(JX429908.1).A substitution mutation at the HBV S gene nt363C →A and nt467G →A were found in the hepatitis B vaccine failure,and amino acid C and W at aa121 and aa156 were deletion in HBsAg of hepatitis B vaccine failure.Conclusions HBV S mutants(nt363C→A and nt467G→A)were found in two hepatitis B vaccine failures.The mutation may result in a conformational change of the HBsAg and hence affecting its antigenicity.更多还原