A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial
A West Nile virus DNA vaccine induces neutralizing antibody in healthy adults during a phase 1 clinical trial
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DOI：
10.1086/523650
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发表时间：
2007-12-15
影响因子：
6.4
通讯作者：
Graham, Barney S.
中科院分区：
文献类型：
--
作者：
Martin, Julie E.;Pierson, Theodore C.;Graham, Barney S.
背景。西尼罗河病毒 (WNV) 是一种蚊媒黄病毒，可导致感染者出现严重的脑膜炎和脑炎。我们在第一个 1 期人体研究中报告了 WNV DNA 疫苗的安全性和免疫原性。方法。在一项针对 15 名健康成年人的开放标签研究中，对编码 WNV NY99 株前膜和包膜糖蛋白的单质粒 DNA 疫苗进行了评估。 12 名受试者完成了 3 剂疫苗接种计划，所有受试者均完成了 32 周的安全性和免疫原性评估。通过酶联免疫吸附测定、中和测定、细胞内细胞因子染色和酶联免疫斑点测定来评估疫苗诱导的免疫反应的发展。结果。该疫苗安全且耐受性良好，没有出现明显的不良事件。在大多数受试者中检测到疫苗诱导的 T 细胞和抗体反应。在完成 3 剂疫苗接种计划的所有受试者中均检测到了西尼罗河病毒的中和抗体，其水平在对马（西尼罗河病毒的偶然自然宿主）的研究中显示具有保护性。结论。有必要对这个用于人类免疫西尼罗病毒的 DNA 平台进行进一步评估。
Background. West Nile virus (WNV) is a mosquitoborne flavivirus that can cause severe meningitis and encephalitis in infected individuals. We report the safety and immunogenicity of a WNV DNA vaccine in its first phase 1 human study.Methods. A single-plasmid DNA vaccine encoding the premembrane and the envelope glycoproteins of the NY99 strain of WNV was evaluated in an open-label study in 15 healthy adults. Twelve subjects completed the 3-dose vaccination schedule, and all subjects completed 32 weeks of evaluation for safety and immunogenicity. The development of a vaccine-induced immune response was assessed by enzyme-linked immunosorbant assay, neutralization assays, intracelluar cytokine staining, and enzyme-linked immunospot assay.Results. The vaccine was safe and well tolerated, with no significant adverse events. Vaccine-induced T cell and antibody responses were detected in the majority of subjects. Neutralizing antibody to WNV was detected in all subjects who completed the 3-dose vaccination schedule, at levels shown to be protective in studies of horses, an incidental natural host for WNV.Conclusions. Further assessment of this DNA platform for human immunization against WNV is warranted.