武汉地区儿童乙型肝炎患者病毒S基因"a"决定簇变异的研究

目的研究武汉地区儿童乙型肝炎患者中乙型肝炎病毒（HBV）S基因变异株的分子流行病学特征。方法通过流行病学调查筛选出30例经乙型肝炎疫苗免疫的儿童乙型肝炎患者及30例未免疫儿童乙型肝炎患者，利用聚合酶链反应（PCR）扩增HBV S基因片段，直接将PCR产物进行DNA序列测定。结果在60例儿童乙型肝炎患者中检测出55例adw血清亚型，其中8例HBV S基因发生氨基酸置换；直接测序检测的已免疫和未免疫儿童乙型肝炎患者S基因氨基酸置换频率分别为20．0％和6．7％，感染基因变异株的患儿发病年龄明显偏大，其疫苗免疫年限均较长。结论本地区流行的乙型肝炎病毒毒株主要为adw血清亚型；乙型肝炎疫苗具有免疫选择表面抗原基因变异株的作用；基因变异株病毒感染有随疫苗免疫年限延长而明显增加的趋势。

Detection of mutants of the "a" determinant region of hepatitis B surface antigen S gene among Wuhan childhood patients

Objective To investigate whether the presence of HBV mutant in vaccinees simply reflects the prevalence of HBV mutant in a specific geographic area or is indeed due to the immune pressure induced by vaccination. Methods HBV S genes were amplified by using polymerase chain reaction (PCR) and DNA sequence analysis of the "a" determinant was performed on sera from 30 childhood patients with immunoprophylaxis and 30 patients without vaccinations. Results Mutations of the "a" determinant were detected in 8 of the 60 patients. They were all of the adw subtype. The prevalence of amino acid substitutions as detected by direct sequencing was higher in those fully-vaccinated than of those not vaccinated. In all 8 vaccinated and also with detectable mutants, the mean age was older than the other vaccinated children. Conclusion The prevalence of mutants is related to HBV subtypes and genotypes. 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. This suggests that new vaccination strategies should be considered.