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尽管进行了免疫预防,但对乙肝表面抗原阳性母亲及其受感染子女进行突变分析。

Mutational analysis of HBs Ag-positive mothers and their infected children despite immunoprophylaxis.

作者信息

Ghaziasadi Azam, Alavian Seyed Moayed, Norouzi Mahdi, Fazeli Zeinab, Jazayeri Seyed Mohammad

机构信息

Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

出版信息

Iran J Allergy Asthma Immunol. 2013 Aug 28;12(4):352-60.

Abstract

Hepatitis B vaccination is safe and effective, although breakthrough infection occasionally occurs in those who receive the vaccine and hepatitis B immunoglobulin (HBIg) prophylaxis. Sequence variation in their antigenic regions is one of the most powerful strategies that are used by viruses to escape recognition by B and T cell-mediated immune responses. The aim of this study was to explore the mutational profile of HBV in vertical transmission.Six HBsAg-positive mothers and their children who developed HBV infection despite immunoprophylaxis were enrolled. After extraction of HBV DNA from sera, the full HBV genome or surface gene was amplified by Gunther and hemi-nested PCR, respectively. After sequencing, the mutational analysis on paired samples between mothers and children were carried out and compared.Different mutations were found in four children, at least, one arose in functional and/or immune epitope activities. Of 30 amino acid changes, 11 (36.6%) were located within the known HBV immune epitopes. In three children, mutations occurred within the "a" determinant region, one mutation (B2) was identical to the mother of patient, an indication of vertical transmission. The other two (B4 and B5) were considered as vaccine escape mutations. Three children harbored wild-type HBsAg, similar to their mothers. Regarding transmission in infected children, the immunoprophylaxis had no effect and failure of vaccination was observed in 2 isolates.These findings emphasized the need for an alternative regimen, such as the administration of boosters or a more effective HBV vaccine for high-risk children who are born to HBsAg-positive mothers.

摘要

乙肝疫苗是安全有效的,尽管在接种疫苗和接受乙肝免疫球蛋白(HBIg)预防的人群中偶尔会发生突破性感染。病毒抗原区域的序列变异是其逃避B细胞和T细胞介导的免疫反应识别的最有效策略之一。本研究的目的是探讨垂直传播中HBV的突变情况。纳入了6名HBsAg阳性母亲及其尽管接受了免疫预防仍发生HBV感染的子女。从血清中提取HBV DNA后,分别通过冈瑟PCR和半巢式PCR扩增完整的HBV基因组或表面基因。测序后,对母婴配对样本进行突变分析并比较。在4名儿童中发现了不同的突变,至少有1个发生在功能和/或免疫表位活性区域。在30个氨基酸变化中,11个(36.6%)位于已知的HBV免疫表位内。在3名儿童中,突变发生在“a”决定簇区域,1个突变(B2)与患者母亲相同,表明存在垂直传播。另外2个(B4和B5)被认为是疫苗逃逸突变。3名儿童携带与母亲相似的野生型HBsAg。关于感染儿童中的传播,免疫预防无效,在2个分离株中观察到疫苗接种失败。这些发现强调了需要一种替代方案,例如对HBsAg阳性母亲所生的高危儿童给予加强免疫或使用更有效的乙肝疫苗。

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