目的 研究应用乙型肝炎病毒表面抗原(HBsAg)-抗体复合物治疗性疫苗(YIC)治疗慢性乙型肝炎患者是否会诱生S基因免疫逃逸变异株的出现。方法 选取5例用30μg或60μgYIC治疗后血清乙型肝炎病毒(HBV)DNA水平下降>2log10、伴有乙型肝炎病毒e抗原(HBeAg)转阴应答,但在随访6个月后病毒DNA水平重复升高的患者作为研究对象,另选取1例对YIC治疗始终无应答患者和1例注射安慰剂患者作为对照,用聚合酶链反应(PCR)方法扩增治疗前(0周)及治疗后(44周)血清中HBV DNA的S基因、前-核心基因、核心基因启动子片段,并进行序列比对分析。结果 S基因“a”决定簇及前-核心基因均未发生变异,但YIC治疗后有3例HBV的核心基因启动子1762/1764位点序列有变异,另有2例在核心基因启动子的其他位点有核苷酸变异。结论 研究显示5例出现病毒重新复制的患者并非由于发生了病毒S基因逃逸变异所致。

Objective To study whether HBsAg-HBIG immunogenic complex therapeutic vaccine (YIC) could induce S gene immune escape mutants.Methods Five chronic hepatitis B patients who had been treated with 6 injections of either 30 or 60 micrograms of YIC were recruited for this study. These patients were those who responded to YIC treatment, shown as a drop in serum HBV DNA virus load >2 log10, with serum HBeAg converted to negative at 24 weeks. However, their virus load rebound at the end of 24 weeks follow-up. As controls, one was a patient who did not respond to YIC treatment and remained serum HBV DNA positive at similar level during and after treatment, while the other one was a patient immunized with the alum placebo. Serum samples before treatment and 6 months after termination of treatment were collected, and DNA extracted. PCR was used to amplify HBV S gene, the precore/core gene and the core promoter regions followed by sequencing.Results In all 7 patients treated with YIC or alum no S gene mutation was found in the “a” determinant, nor was precore stop codon mutation detected. However, three patients had mutations in the 1762/1764 core-promoter region, other two patients had mutations in the core promoter region other than the 1762/1764 double mutation.Conclusion The rebound of HBV replication in five YIC-treated patients was not due to the emergence of HBV S immune-escape mutants. if(document.getElementById('ChDivSummary').innerHTML!=""){CutSpan('ChDivSummary',500);DisplaySpanDiv('ChDivSummary');ClearSummaryOnLoad('SummaryLinkChID','SummaryLinkEnID');}else{CutSpan('EnDivSummary',1000);DisplaySpanDiv('EnDivSummary');ClearSummaryOnLoad('SummaryLinkEnID','SummaryLinkChID');}