Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan
Changes of hepatitis B surface antigen variants in carrier children before and after universal vaccination in Taiwan
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DOI：
10.1002/hep.510300511
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发表时间：
1999-11-01
期刊：
影响因子：
13.5
通讯作者：
Chen, HL
中科院分区：
文献类型：
--
作者：
Hsu, HY;Chang, MH;Chen, HL
在接种疫苗的儿童中发现的乙型肝炎表面抗原 (HBsAg) 决定簇突变体对疫苗接种计划的长期成功构成潜在威胁。我们检查了乙型肝炎病毒 (HBV) DNA 阳性儿童中 HBsAg 决定簇（残基 110-160）的突变体，这些儿童是在台北进行的之前（1984 年）、全民疫苗接种开始后 5 年（1989 年）和 10 年（1994 年）后进行的血清调查中发现的。在 3 次调查的 HBV DNA 阳性儿童中，决定性突变体的患病率从 1984 年的 103 名儿童中的 8 名（7.8%）增加到 1989 年的 51 名儿童中的 10 名（19.6%）和 1994 年的 32 名儿童中的 9 名（28.1%），并且在完全接种疫苗的儿童中高于未接种疫苗的儿童（12/33 与 15/153，P = .0003）。变体的大多数氨基酸变化集中在残基 125-129 和 140-149 处。在所有 27 名携带可检测突变体的儿童中，接种疫苗的儿童的平均年龄比未接种疫苗的儿童年轻（4.8 +/- 3.8 岁 vs. 7.9 +/- 2.3 岁，P < .05）；与未接种疫苗的人相比，在局部亲水性最大的区域（残基 140-149）发生突变的频率更高（10/12 与 6/15；P = .0253）。 1994年的调查发现了更多的突变残基和更多的中和表位突变，如N146、C147、T148和C149。接种疫苗的儿童可能通过垂直或水平传播感染变异病毒。普遍疫苗接种加速了 HBsAg 的积累，HBsAg 是一种决定性突变体，其氨基酸变化对于已接种疫苗的儿童成为携带者的免疫逃逸至关重要，这表明应考虑新的疫苗接种策略。
Mutants of a determinant of hepatitis B surface antigen (HBsAg) identified in vaccinated children pose a potential threat to long-term success of vaccination programs. We examined the mutants of a determinant (residues 110-160) of HBsAg in hepatitis B virus (HBV) DNA-positive children identified during previous serosurveys in Taipei undertaken just before (1984), 5 years after (1989), and 10 years after (1994) universal vaccination began. In HBV DNA-positive children from 3 surveys, the prevalence of a determinant mutants increased from 8 of 103 (7.8%) in 1984 to 10 of 51 (19.6%) in 1989 and 9 of 32 (28.1%) in 1994 and was higher in those fully-vaccinated than unvaccinated (12/33 vs. 15/153, P = .0003). Most amino acid changes of the variants clustered in residues 125-129 and 140-149. In all 27 children with detectable mutants, the mean age of those vaccinated was younger than those unvaccinated (4.8 +/- 3.8 vs. 7.9 +/- 2.3 yrs, P < .05); and mutations occurred in a region with greatest local hydrophilicity (residues 140-149) more frequently in those vaccinated than in those unvaccinated (10/12 vs. 6/15; P = .0253). More mutated residues and more mutations at neutralizing epitopes, such as N146, C147, T148, and C149, were found in the 1994 survey. Vaccinated children may contract variant infections through vertical or horizontal transmission. Universal vaccination has accelerated an accumulation of HBsAg a determinant mutants with amino acid changes critical for immune escape in vaccinated children who became carriers, suggesting that new vaccination strategies should be considered.