美国针对 2009 年甲型 H1N1 流感的单次疫苗接种后的免疫反应：两项随机对照 2 期试验的初步报告。
Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials.
机构信息
Clinical Development Department, Sanofi-Pasteur, Lyon, France.
出版信息
Lancet. 2010 Jan 2;375(9708):41-8. doi: 10.1016/S0140-6736(09)62026-2. Epub 2009 Dec 15.
BACKGROUND
Data are needed from large clinical trials of paediatric, adult, and elderly people to find the appropriate antigen dose and vaccination schedule for the 2009 pandemic influenza A H1N1. We therefore report preliminary safety and immunogenicity results after one injection of a licensed monovalent pandemic H1N1 vaccine in the USA.
METHODS
We randomly assigned healthy children (aged 6-35 months and 3-9 years) and adults (18-64 years and >or=65 years) to vaccine containing per dose 7.5 microg (children and adults), 15 microg (children and adults), or 30 microg (adults only) haemagglutinin in two placebo-controlled, observer-masked, multicentre phase 2 studies done in the USA. Participants were allocated with an interactive voice-response system or computer-generated randomisation lists with opaque scratchable patches. Primary outcome was haemagglutination inhibition antibody response 21 days after the first of two planned vaccinations (interim analysis of studies in progress). Analyses were by full-analysis set. The trials are registered with ClinicalTrials.gov as NCT00953524 and NCT00952419.
FINDINGS
410 of 423 children and 724 of 750 adults given an active vaccine, and 50 of 51 children and 95 of 99 adults given placebo were assessed for immunogenicity on day 21. After active vaccination, 45 of 101 (45%; 95% CI 35-55) to 47 of 94 (50%; 40-61) infants aged 6-35 months, 75 of 109 (69%; 59-77) to 80 of 106 (75%; 66-83) 3-9-year-old children, 134 of 141 (95%; 90-98) to 144 of 144 (100%; 98-100) of 18-64-year-old adults, and 93 of 100 (93%; 86-96) to 93 of 98 (95%; 89-98) elderly adults were seroprotected (proportion with titres >or=1:40). No vaccine-related serious adverse events occurred. Injection-site and systemic reactions were reported by up to about 50% of every age and vaccine group, with no noticeable differences between vaccine and placebo groups.
INTERPRETATION
One dose of vaccine was highly immunogenic in adults, suggesting that it afforded sufficient protection against this pandemic influenza A H1N1 virus. Two doses of vaccine will probably be needed in children younger than 9 years. Safety and reactogenicity of the vaccine were acceptable and similar to those of seasonal vaccine.
FUNDING
Office of the Assistant Secretary for Preparedness and Response, and Biomedical Advanced Research and Development Authority.
背景
需要从儿科、成人和老年人群的大型临床试验中获取数据，以找到适合 2009 年大流行的甲型 H1N1 流感的适当抗原剂量和疫苗接种方案。因此，我们报告了在美国进行的一项已许可的单价大流行 H1N1 疫苗的初步安全性和免疫原性结果，仅注射一次。
方法
我们将健康儿童（6-35 个月和 3-9 岁）和成人（18-64 岁和≥65 岁）随机分配至含有 7.5 μg（儿童和成人）、15 μg（儿童和成人）或 30 μg（仅成人）血凝素的疫苗中，在两项在美国进行的安慰剂对照、观察者设盲、多中心 2 期研究中进行。参与者通过交互式语音响应系统或使用带有不透明刮擦补丁的计算机生成的随机列表进行分配。主要终点是两次计划接种疫苗后的第 21 天的血凝抑制抗体反应（正在进行的研究的中期分析）。分析采用全分析集。这些试验在 ClinicalTrials.gov 上注册为 NCT00953524 和 NCT00952419。
发现
423 名儿童中有 410 名和 750 名成人中有 724 名接受了活性疫苗，而 51 名儿童中有 50 名和 99 名成人中有 95 名接受了安慰剂，在第 21 天进行了免疫原性评估。接种疫苗后，6-35 个月大的婴儿中有 45/101（45%；95%CI 35-55）至 47/94（50%；40-61），3-9 岁的儿童中有 75/109（69%；59-77）至 80/106（75%；66-83），18-64 岁的成年人中有 134/141（95%；90-98）至 144/144（100%；98-100），100 岁的成年人中有 93/100（93%；86-96）至 93/98（95%；89-98）对甲型 H1N1 流感病毒具有血清保护性（滴度>或=1：40 的比例）。没有与疫苗相关的严重不良事件发生。每个年龄组和疫苗组中，高达约 50%的人报告了注射部位和全身反应，疫苗组与安慰剂组之间没有明显差异。
解释
一剂疫苗在成年人中具有高度的免疫原性，这表明它对这种大流行的甲型 H1N1 病毒提供了足够的保护。9 岁以下的儿童可能需要接种两剂疫苗。疫苗的安全性和反应原性可接受，与季节性疫苗相似。
资金
助理部长准备和应对办公室和生物医学高级研究与发展管理局。
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