Altered antigenicity of 'a' determinant variants of hepatitis B virus
Altered antigenicity of 'a' determinant variants of hepatitis B virus
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DOI：
10.1099/0022-1317-78-10-2639
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发表时间：
1997-10-01
影响因子：
3.8
通讯作者：
Ho, MS
中科院分区：
文献类型：
--
作者：
Chiou, HL;Lee, TS;Ho, MS
乙型肝炎病毒 (HBV) 表面抗原 (HBsAg) 的“a”决定簇是诊断和免疫预防最重要的目标。在台湾完全接种疫苗的儿童中，已发现了几种在“a”决定簇内带有点突变的 HBV 变异体。我们通过在巴斯德毕赤酵母中克隆和表达突变体 S 抗原，研究了每种突变对 S 蛋白抗原性质的影响。四种变体，Ser-126、His-129、Arg-129 和 Arg-145，都表现出不同程度的 HBsAg 与几种单克隆抗体结合的改变。与其他变体相比，Arg-145（一种充分表征的免疫逃逸突变体）和 Arg-129 对所有单克隆抗体的结合能力最低。与 Arg-145 类似，Arg-129 变体可以从接种疫苗的儿童和未接种疫苗的成人中分离出来，因此代表了具有改变的“a”决定簇的自然发生的突变体。由于疫苗接种产生的针对野生型乙型肝炎病毒的免疫压力，这些抗原性改变的“a”决定簇变体是否可能逐渐成为主要的流行毒株，仍有待监测。
The 'a' determinant of hepatitis B virus (HBV) surface antigen (HBsAg) is the most important target for diagnosis and immunoprophylaxis. Several HBV variants with point mutations within the 'a' determinant have been identified among fully vaccinated children in Taiwan. We investigated the effect of each of these mutations on the antigenic nature of the S protein by cloning and expression of the mutant S antigens in Pichia pastoris. Four variants, Ser-126, His-129, Arg-129 and Arg-145, all exhibited various degrees of altered binding of HBsAg to several monoclonal antibodies. Arg-145, a well-characterized immune escape mutant, and Arg-129 had the lowest binding capacities to all monoclonal antibodies as compared with other variants. Similar to Arg-145, the Arg-129 variant could be isolated from both vaccinated children and unvaccinated adults, thus representing a naturally occurring mutant with an altered 'a' determinant. Whether these 'a' determinant variants with altered antigenicity might gradually become major circulating strains, as a consequence of the immune pressure against the wild-type HBV created by vaccination, remains to be monitored.