Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial
Efficacy and safety of a recombinant hepatitis E vaccine in healthy adults: a large-scale, randomised, double-blind placebo-controlled, phase 3 trial
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DOI：
10.1016/s0140-6736(10)61030-6
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发表时间：
2010-09-11
期刊：
影响因子：
168.9
通讯作者：
Xia, Ning-Shao
中科院分区：
文献类型：
--
作者：
Zhu, Feng-Cai;Zhang, Jun;Xia, Ning-Shao
背景 血清流行率数据表明，世界上三分之一的人口已感染戊型肝炎病毒。我们的目的是在一项随机、双盲、安慰剂对照、3 期试验中评估重组戊型肝炎疫苗 HEV 239（Hecolin；厦门 Innovax Biotech，中国厦门）的有效性和安全性。方法中国江苏省 16-65 岁的健康成年人以 1:1 的比例随机分配接受三剂 HEV 239（30 jig 纯化的重组戊型肝炎抗原吸附于悬浮于 0.5 mL 缓冲盐水中的 0.8 mg 氢氧化铝）或安慰剂（乙型肝炎疫苗）在 0、1 和 6 个月时肌肉注射。随机化是通过计算机生成的排列块完成的，并按年龄和性别分层。参与者被随访了 19 个月。主要终点是从第三次注射后第 31 天起的 12 个月内预防戊型肝炎。分析基于按照方案接受全部三种剂量的参与者。研究参与者、护理人员和研究人员都对分组和疫苗分配情况不知情。该试验在 ClinicalTrials.gov 注册，编号为 NCT01014845。结果 11165 名试验参与者接受了戊型肝炎病毒 IgG 检测，其中 5285 名（47%）戊型肝炎病毒血清呈阳性。参与者被随机分配到疫苗组 (n=56302) 或安慰剂组 (n=56302)。疫苗组的 48 693 名参与者 (86%) 和安慰剂组的 48 663 名参与者 (86%) 接受了三剂疫苗，并被纳入主要疗效分析。在接受第三剂疫苗 30 天后的 12 个月内，安慰剂组中符合方案的 15 名参与者出现了戊型肝炎，而疫苗组中则没有。三次接种后的疫苗效力为 100.0% (95% CI 72.1-100.0)。疫苗引起的不良反应很少且轻微。未发现与疫苗接种相关的严重不良事件。 解读 HEV 239 在中国普通人群（包括 16-65 岁的男性和女性）中具有良好的耐受性并能有效预防戊型肝炎。
Background Seroprevalence data suggest that a third of the world's population has been infected with the hepatitis E virus. Our aim was to assess efficacy and safety of a recombinant hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled, phase 3 trial.Methods Healthy adults aged 16-65 years in, Jiangsu Province, China were randomly assigned in a 1:1 ratio to receive three doses of HEV 239 (30 jig of purified recombinant hepatitis E antigen adsorbed to 0.8 mg aluminium hydroxide suspended in 0.5 mL buffered saline) or placebo (hepatitis B vaccine) given intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-generated permuted blocks and stratified by age and sex. Participants were followed up for 19 months. The primary endpoint was prevention of hepatitis E during 12 months from the 31st day after the third dose. Analysis was based on participants who received all three doses per protocol. Study participants, care givers, and investigators were all masked to group and vaccine assignments. This trial is registered with ClinicalTrials.gov, number NCT01014845.Findings 11165 of the trial participants were tested for hepatitis E virus IgG, of which 5285 (47%) were seropositive for hepatitis E virus. Participants were randomly assigned to vaccine (n=56302) or placebo (n=56302). 48 693 (86%) participants in the vaccine group and 48 663 participants (86%) in the placebo group received three vaccine doses and were included in the primary efficacy analysis. During the 12 months after 30 days from receipt of the third dose 15 per-protocol participants in the placebo group developed hepatitis E compared with none in the vaccine group. Vaccine efficacy after three doses was 100.0% (95% CI 72.1-100.0). Adverse effects attributable to the vaccine were few and mild. No vaccination-related serious adverse event was noted.Interpretation HEV 239 is well tolerated and effective in the prevention of hepatitis E in the general population in China, including both men and women age 16-65 years.