Hepatitis B virus surface gene mutants in immunoprophylaxis-failed infants from Southern China
Hepatitis B virus surface gene mutants in immunoprophylaxis-failed infants from Southern China
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DOI：
10.1002/jmv.25430
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发表时间：
2019-06-01
影响因子：
12.7
通讯作者：
Chen, Weixian
中科院分区：
文献类型：
--
作者：
Huang, Yong;Wang, Bo;Chen, Weixian
乙型肝炎病毒（HBV）疫苗接种被认为是预防乙型肝炎病毒母婴传播的最有力工具。 1992年，中国启动了婴儿乙肝疫苗全民接种计划。本研究的目的是调查免疫预防失败的婴儿、未接种疫苗的婴儿患者和成人慢性乙型肝炎 (CHB) 患者（未经核苷类似物治疗）的 HBV 表面抗原 (HBsAg) 变异。免疫预防失败的婴儿是从两个中心（广东和重庆，代表中国南方）招募的。采用酶联免疫吸附法检测乙型肝炎病毒血清标志物，包括乙型肝炎表面抗原（HBsAg）、戊型肝炎e抗原（HBeAg）和核心抗原。通过定量聚合酶链反应检测HBV DNA载量。扩增并分析编码 HBsAg 的核苷酸序列。免疫预防失败的婴儿中“a”决定簇第二环（局部亲水性较大的区域）内氨基酸取代的频率明显高于未接种疫苗的婴儿患者和成人 CHB 患者（9.6% vs 0% vs 3.8%；chi(2) = 7.454；P = 0.024）。免疫预防失败婴儿中超过 50% (52.8%) 的氨基酸替换位于 B 细胞表位，而成人 CHB 患者中 64.6% 的氨基酸替换位于 CTL 细胞表位。 HBeAg 阴性患者的 CTL 和 Th 细胞表位替换频率较高，在主要亲水区发生替换的免疫预防失败婴儿患者中，丙氨酸转氨酶水平较高（68.6 +/- 111.5 vs 62.1 +/- 132.2；P = 0.026），DNA 载量较低（7.03 +/- 1.72 vs 7.82 +/-）。 1.73；P<0.001）。总之，我们的结果观察到疫苗失败婴儿中疫苗诱导的免疫选择压力，“a”决定簇的替换，特别是G145替换仍然是最稳定和显着的疫苗逃逸位点。
Hepatitis B virus (HBV) vaccination was considered the most powerful tool for prevention of HBV transmission from mother to infant. In 1992, a universal HBV vaccination program for infants was launched in China. The aim of this study was to investigate the HBV surface antigen (HBsAg) variations in immunoprophylaxis-failed infants, vaccine free infant patients and adult chronic hepatitis B (CHB) patients (without nucleoside analog treatment). Immunoprophylaxis-failed infants were recruited from two centers (Guangdong and Chongqing, representing Southern China). HBV serum markers, including HBsAg, hepatitis e antigen (HBeAg), and core antigen, were detected by the enzyme-linked immunosorbent assay. HBV DNA load was detected by quantitative polymerase chain reaction. Nucleotide sequences encoding HBsAg were amplified and analyzed. Frequencies of amino acid substitutions within the second loop of "a" determinant (region with greater local hydrophilicity) in immunoprophylaxis-failed infants were clearly higher than the unvaccinated infant patients and adult CHB patients (9.6% vs 0% vs 3.8%; chi(2) = 7.454; P = 0.024). More than 50% (52.8%) aa substitutions in immunoprophylaxis-failed infants were located in B cell epitopes, while 64.6% aa substitutions in adult CHB patients were located in CTL cell epitopes. HBeAg negative patients had higher substitution frequency in CTL and Th cell epitopes, and in immunoprophylaxis-failed infant patients with substitution in major hydrophilic region region had a higher alanine aminotransferase level (68.6 +/- 111.5 vs 62.1 +/- 132.2; P = 0.026), and lower DNA load (7.03 +/- 1.72 vs 7.82 +/- 1.73; P < 0.001). In conclusion, our results observed vaccine-induced immune selection pressure in vaccine failed infants, substitutions in "a" determinant, especially the G145 substitution was still the most stable and remarkable site of vaccine escape.