单纯乙型肝炎疫苗免疫后携带者表面抗原氨基酸置换的频率和特征

Prevalence of mutants in the α determinant region of hepatitis B surface antigen among Chinese carriers after receiving only active postexposure immunoprophylaxis

目的 掌握中国单纯乙型肝炎疫苗免疫后携带者和未免疫携带者表面抗原基因变异的流行状况及特点。方法 以直接测序和特异基因序列固相聚合酶链反应 (SS SPPCR)方法 ,分别检测97例单纯乙型肝炎疫苗免疫后携带者、88例未免疫育龄妇女和 95例未免疫儿童携带者 ,乙型肝炎病毒α抗原决定簇氨基酸置换的流行率。结果 直接测序检测的乙型肝炎疫苗免疫后携带者氨基酸置换流行率显著高于未免疫育龄妇女和儿童携带者对照 ,流行率分别为 30 9% (30 97) ,10 2 % (9 88)和5 3% (5 95 )。 145、12 6和 133是最常见的氨基酸酸置换位点。应用更为敏感的SS SPPCR法分别检测145和 12 6位氨基酸点突变的流行率 ,各组间差异不明显 ,其中 145位氨基酸置换的流行率分别为39 2 % ,33 0 %和 32 6%。经直接测序法检测 ,免疫后携带者基因变异流行率高于未免疫携带者 5 41倍。按基因型和血清亚型分层分析 ,基因型B和adw2血清亚型携带者受免疫选择后出现基因变异的风险显著较高 ,分别为 34 5 5和 33 39;而基因型C和adr血清亚型携带者基因变异风险较低 ,分别为2 73和 2 45。结论 单纯乙型肝炎疫苗具有免疫选择表面抗原基因变异株的作用 ;基因变异株在未免疫携带者中主要是弱势准种 ;基因变异风险与病毒基因型和血清亚型?

Objective To determine the frequency of hepatits B surface antigen (HBsAg) mutations in the α determinant region among children who developed chronic hepatits B virus(HBV) infection after receiving only active postexposure immunoprophylaxis.Methods HBsAg mutations were determined by PCR directed nucleotide sequencing and sequence specific solid phase PCR analysis(SS SPPCR) for 97 Chinese carrier cases after hepatitis B vaccination,for 88 children born aged women controls,and for 95 population based children controls.Results Prevalence of amino acid substitutions as detected by direct sequencing among carrier cases,women controls,and children controls were 30.9%,10.2%,and 5.3%,respectively.The most frequent amino acid substitutions observed were at residues 145,126,and 133.However,there was no difference in the prevalence of 145 and 126 amino acid mutants as detected by a sensitive SS SPPCR method between carrier cases and controls.The prevalence of 145 Arg and 145 Ala mutants that were detected by SS SPPCR was 39.2%,33.0% and 32.6% among carrier cases,women controls,and children controls,respectively.The total odds ratio was 5.41 for mutants detected by direct sequencing.Odds ratio were 34.55 and 33.39 among adw2 subtype and genotype B subjects for mutants detected by direct sequencing,respectively.Conclusion The results show that hepatits B virus mutants in the a determinant are fairly consistent observed but without immune selective pressures;HBV variant strains may pre existent as minor quasispecies.The prevalence of mutants is related to HBV subtypes and genotypes.