Quasispecies characters of hepatitis B virus in immunoprophylaxis failure infants
Quasispecies characters of hepatitis B virus in immunoprophylaxis failure infants
复制标题
免疫预防失败婴儿乙型肝炎病毒准种特征
DOI：
10.1007/s10096-018-3235-5
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发表时间：
2018-06-01
影响因子：
4.5
通讯作者：
Long, Quanxin
中科院分区：
文献类型：
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作者：
Wang, Xin;Deng, Wanyan;Long, Quanxin
接种B型肝炎疫苗可预防80-95%的传播，并降低儿童中HBV的发病率。据报道，HBV表面抗原（HBsAg）α决定簇的变异是疫苗或抗体逃逸的最常见原因。关于逃逸突变体是否在感染的婴儿中重新出现，或者突变体是否在母体中预先存在，随后在免疫压力下在婴儿中进行选择性复制，存在相互矛盾的证据。在这里，我们报告了近65%（55/85）的儿童患者疫苗接种失败，桑格测序显示，在一个决定簇中没有氨基酸取代。我们进一步采用基于Illumina测序平台的方法检测4名免疫预防失败的婴儿及其母亲的HBV准种。在我们的数据中，位于一个决定簇的氨基酸替换率相对较低（< 10%），I/T126 A、C124 S、F134 Y、K141 Q、Q129 H、D144 A、G145 V和N146 K，与它们的母体没有统计学差异，证明这些疫苗逃逸突变体作为微小变异体先存在于母体。此外，生物信息学分析表明，高变异表位（母婴间氨基酸差异> 20%）与相关HLA分子的结合亲和力普遍降低，这些免疫逃逸的痕迹表明免疫压力在所有样本中存在且有效。
Hepatitis B vaccination prevents 80-95% of transmission and reduces the incidence of HBV in children. The variations in the a determinant of HBV surface antigen (HBsAg) have been reported to be the most prevalent cause for vaccine or antibody escape. There is a conflicting evidence on as to whether escape mutants arise de novo in infected infants or whether the mutants, that have preexisted maternally, subsequently undergo selective replication in the infant under immune pressure. Here, we report that nearly 65% (55 of 85) vaccination failure in child patients has no amino acid substitution in a determinant as seen by Sanger sequencing. We further employed an Illumina sequencing platform-based method to detect HBV quasispecies in four immunoprophylaxis failure infants and their mothers. In our data, the substitution rate of amino acid located at a determinant is relatively low (< 10%), I/T126A, C124S, F134Y, K141Q, Q129H, D144A, G145V, and N146K, which showed no statistical difference to their mothers, proving that these vaccine escape mutants preexist maternally as minor variants. Besides that, bioinformatical analysis showed that the binding affinity of high variation epitopes (amino acid divergence in mother and their infants > 20%) to related HLA molecules was generally decreased, these traces of immune escape suggesting that immune pressure was present and was effective in all samples.