Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase I randomised controlled trial
Safety and immunogenicity of an inactivated adjuvanted whole-virion influenza A (H5N1) vaccine: a phase I randomised controlled trial
复制标题
DOI：
10.1016/s0140-6736(06)69294-5
复制
发表时间：
2006-09-16
期刊：
影响因子：
168.9
通讯作者：
Yin, Weidong
中科院分区：
文献类型：
--
作者：
Lin, Jiangtao;Zhang, Jiansan;Yin, Weidong
背景甲型禽流感病毒H5N1已引起广泛感染，在家禽和野生鸟类以及人类中造成严重疾病或死亡。这种病毒有可能成为大流行威胁，许多国家正在开发H5N1疫苗。我们的目的是评估一种灭活佐剂全病毒粒子H5N1疫苗的安全性和免疫原性。方法采用分层随机、安慰剂对照、双盲I期临床试验，纳入120名年龄在18-60岁的志愿者。在第0天和第28天，志愿者被分配接受两剂安慰剂（n=24）或每剂含1.25 μ g（24）、2.5 μ g（24）、5 μ g（24）或10 μ g（24）的灭活甲型流感（H5N1）全病毒粒子疫苗和氢氧化铝佐剂。在第0、14、28、42和56天采集血清样本进行血凝抑制和病毒中和试验。该试验已在ClinicalTrials.gov注册中心注册，注册号为NCT00356798。所有四种疫苗制剂均具有良好的耐受性。没有严重的不良事件报道，大多数局部和全身反应是轻微和短暂的。所有配方均在第一剂后诱导抗体反应；两剂疫苗后，10 μ g组免疫反应最高，血清阳性率为78%。2人退出：1人在1.25 μ g组（撤回同意），1人在10 μ g组（停止）；有一个人也被排除在最终分析之外。两剂佐剂10 μ g灭活H5N1全病毒粒子疫苗方案符合季节性流感疫苗年度许可的所有欧洲监管要求。低剂量的这种疫苗可以达到与佐剂或非佐剂分裂病毒颗粒疫苗相同的免疫反应。使用全病毒粒子疫苗可能更适合世卫组织为预防流感大流行而建议的抗原保留策略。
Background Avian influenza A virus H5N1 has caused widespread infections that have resulted in severe disease or death in poultry and wild birds as well as human beings. This virus has the potential to emerge as a pandemic threat and H5N1 vaccines are being developed in many countries. Our aim was to assess the safety and immunogenicity of an inactivated adjuvanted whole-virion H5N1 vaccine.Methods A stratified randomised, placebo-controlled, double-blind phase I clinical trial was done in 120 volunteers aged 18-60 years. Volunteers were assigned to receive two doses of placebo (n=24) or an inactivated whole-virion influenza A (H5N1) vaccine with 1.25 mu g (24), 2.5 mu g (24), 5 mu g (24), or 10 mu g (24) haernagglutinin per dose with aluminium hydroxide adjuvant on day 0 and 28. Serum samples were obtained on day 0, 14, 28, 42, and 56 for haemagglutination inhibition and virus neutralisation assays. This trial is registered with the ClinicalTrials.gov registry with the number NCT00356798.Findings All four formulations of vaccines were well tolerated. No serious adverse event was reported and most local and systemic reactions were mild and transient. All formulations induced antibody responses after the first dose; the highest immune response of 78% seropositivity was seen in the 10 mu g group after two vaccine doses. Two individuals dropped out: one in the 1.25 mu g group (withdrew consent) and one in the 10 mu g group (discontinued); one individual was also excluded from the final analysis.Interpretation A two-dose regimen of an adjuvanted 10 mu g inactivated whole-virion H5N1 vaccine met all European regulatory requirements for annual licensing of seasonal influenza vaccine. Lower doses of this vaccine could achieve immune responses equivalent to those elicited by adjuvanted or non-adjuvanted split-virion vaccines. The use of a whole virion vaccine could be more adaptable to the antigen-sparing strategy recommended by WHO for protection against an influenza pandemic.