深圳市乙肝疫苗免疫失败者S基因分析

目的了解乙肝疫苗免疫失败者的HBVS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2564份受检者中．筛选出2例（0．78％e）HBsAg（-）／HBeAg（＋）／HBcAb（＋）乙肝疫苗免疫失败者（HBsl、HBs2），经HBVDNA荧光定量PCR检测和HBVS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，HBsAg121位和156位氨基酸C和w缺失。结论乙肝疫苗免疫失败者HBVS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。

Analysis of hepatitis B virus S gene of hepatitis B vaccine failures from Shenzhen city

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%o） 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.