DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial
DNA vaccination protects against an influenza challenge in a double-blind randomised placebo-controlled phase 1b clinical trial
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DOI：
10.1016/j.vaccine.2009.02.061
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发表时间：
2009-04-21
期刊：
影响因子：
5.5
通讯作者：
Loudon, Peter T.
中科院分区：
文献类型：
--
作者：
Jones, Suzanne;Evans, Kirsten;Loudon, Peter T.
背景：我们开发了一种流感三价 DNA 疫苗，由使用 PMED (TM)（颗粒介导表皮递送）递送的不同季节性流感病毒株表达血凝素的三个质粒组成。我们着手确定这种疫苗（含有或不含分子佐剂 DNA 编码免疫刺激不稳定毒素 (DEI-LT)）是否可以保护受试者免受受控流感病毒的攻击。方法：对健康成年受试者进行 A/H3 巴拿马/2007/99 流感感染的易感性筛查，然后接种 4 μg 三价流感 DNA 疫苗，2 μg 三价流感 DNA 疫苗加 DEI-LT 或安慰剂。对疫苗接种的安全性和血清学反应进行了评估，并在第 56 天对受试者进行 A/H3 巴拿马/2007/99 病毒攻击。结果：用 4 μg 三价或 2 μg 三价/DEI-LT 进行疫苗接种具有良好的耐受性，并诱导对三种流感病毒疫苗株中的两种产生抗体反应。攻击后，与安慰剂 (N = 27) 相比，4 μg 三价组的受试者 (N = 27) 表现出疾病症状和病毒脱落减少，“任何有或没有发烧的疾病”的总体疫苗效力为 41%（95% 置信区间 (CI) = -1.5, 67.7），“上呼吸道感染”的总体疫苗效力为 53%（95% CI = 8.0， 77.7).结论：得出的结论是，用 4 μg 三价流感 DNA 疫苗接种 PMED 是安全的，并引发免疫反应，保护人类受试者免受流感的侵害；这是第一份通过 DNA 疫苗接种保护人类受试者免受疾病侵害的报告。 (C) 2009 Elsevier Ltd. 保留所有权利。
Background: We have developed a Trivalent DNA vaccine for influenza consisting of three plasmids expressing haemagglutinin from different seasonal influenza virus strains delivered using PMED (TM) (particle mediated epidermal delivery). We set out to determine whether this vaccine (with and without a molecular adjuvant DNA Encoded Immunostimulator-Labile Toxin (DEI-LT)) could protect subjects from a controlled influenza virus challenge.Methods: Healthy adult subjects were screened for susceptibility to infection with influenza A/H3 Panama/2007/99 then vaccinated with 4 mu g Trivalent influenza DNA vaccine, 2 mu g Trivalent influenza DNA vaccine plus DEI-LT or placebo. Safety and serological responses to vaccination were assessed and on Day 56 subjects were challenged with A/H3 Panama/2007/99 virus.Results: Vaccination with 4 mu g Trivalent or 2 mu g Trivalent/DEI-LT was well tolerated and induced antibody responses to two of the three influenza virus vaccine strains. Post challenge, subjects in the 4 mu g Trivalent group (N= 27) showed reductions in disease symptoms and viral shedding compared to placebo (N = 27), with an overall vaccine efficacy of 41% (95% confidence interval (CI) = -1.5, 67.7) for 'Any illness with or without fever' and 53% for 'Upper respiratory tract infection' (95% CI = 8.0, 77.7).Conclusion: It was concluded that PMED vaccination with 4 mu g Trivalent influenza DNA vaccine was safe and elicited immunological responses that protected human subjects from influenza; this is the first report of protection of human subjects from disease by DNA vaccination. (C) 2009 Elsevier Ltd. All rights reserved.