Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials
Immune response after a single vaccination against 2009 influenza A H1N1 in USA: a preliminary report of two randomised controlled phase 2 trials
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DOI：
10.1016/s0140-6736(09)62026-2
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发表时间：
2010-01-02
期刊：
影响因子：
168.9
通讯作者：
Denis, Martine
中科院分区：
文献类型：
--
作者：
Plennevaux, Eric;Sheldon, Eric;Denis, Martine
背景：为确定2009年甲型H1N1流感大流行的适当抗原剂量和疫苗接种计划，需要从儿童、成人和老年人的大型临床试验中获得数据。因此，我们报告在美国一次注射许可的单价H1N1大流行性流感疫苗后的初步安全性和免疫原性结果。在美国进行的两项安慰剂对照、观察者屏蔽、多中心ii期研究中，我们随机分配健康儿童（6-35个月和3-9岁）和成人（18-64岁和>= 65岁）接种每剂量含有7.5 μ g（儿童和成人）、15 μ g（儿童和成人）或30 μ g（仅成人）血凝素的疫苗。参与者被分配到交互式语音应答系统或计算机生成的随机列表中，这些列表带有不透明的可刮擦补丁。主要结局是在两次计划接种疫苗中的第一次接种后21天的血凝抑制抗体应答（正在进行的研究的中期分析）。采用全分析集进行分析。这些试验已在ClinicalTrials.gov注册为NCT00953524和NCT00952419。结果：在第21天，423名儿童中有410人接种了活疫苗，750名成人中有724人接种了活疫苗，51名儿童中有50人接种了安慰剂，99名成人中有95人接种了安慰剂。主动接种疫苗后，6-35月龄婴儿101例中有45例（45%;95% CI 35-55）至94例中有47例（50%;40-61），3-9岁儿童109例中有75例（69%;59-77）至80例（75%;66-83），18-64岁成人141例中有134例（95%;90-98）至144例（100%;98-100），老年人100例中有93例（93%;86-96）至93例（95%;89-98）得到免疫保护（滴度比例2:1:40）。未发生与疫苗相关的严重不良事件。在每个年龄和疫苗组中，高达50%的人报告了注射部位和全身反应，疫苗组和安慰剂组之间没有明显差异。一剂疫苗在成人中具有高度免疫原性，表明它对甲型H1N1流感大流行病毒提供了足够的保护。9岁以下的儿童可能需要两剂疫苗。疫苗的安全性和反应原性可接受，与季节性疫苗相似。负责准备和应对的助理部长资助办公室，以及生物医学高级研究和发展管理局。
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 >= 65 years) to vaccine containing per dose 7.5 mu g (children and adults), 15 mu g (children and adults), or 30 mu g (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 2:1:40). 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.