Optimizing particle-mediated epidermal delivery of an influenza DNA vaccine in ferrets.

Optimizing particle-mediated epidermal delivery of an influenza DNA vaccine in ferrets.
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优化雪貂体内流感 DNA 疫苗的颗粒介导表皮递送。

DOI:
10.1007/978-1-62703-110-3_19
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发表时间:
2013
期刊:
Methods in molecular biology (Clifton, N.J.)
影响因子:
--
通讯作者:
Fuller,DeborahH
Fuller,DeborahH
中科院分区:
--
文献类型:
--
作者:
Yager,EricJ;Stagnar,Cristy;Gopalakrishnan,Ragisha;Fuller,JamesT;Fuller,DeborahH

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粒子介导的DNA递送技术(“基因枪”)已在动物和临床研究中显示为增加DNA疫苗的免疫原性和保护效力的有效手段。在不同动物模型中优化颗粒介导的表皮递送(PMED)疫苗接种的主要目标是实现DNA包被的金珠递送到活表皮中。影响这一结果的两个关键参数包括递送压力和DNA递送的解剖部位,递送压力控制珠粒进入皮肤的穿透力。尽管雪貂已被广泛用作人类流感感染的实验模型,但很少有研究调查PMED DNA疫苗接种在雪貂中诱导保护性免疫应答的能力。在这里,我们描述了使用PowderJect XR 1基因递送在雪貂中优化DNA疫苗递送的方法。我们首先评估射击压力对DNA包被的金珠进入所需表皮层的递送和靶位点处DNA疫苗报告基因表达的程度的影响。其次,我们通过检测对模式抗原流感病毒血凝素和B型肝炎核心抗原的血清抗体应答来评估疫苗接种部位(皮肤或舌头)对DNA疫苗免疫原性的影响。这些研究的结果支持在雪貂中使用PowderJect XR 1装置,用于研究针对临床重要疾病(如流感病毒感染)的预防性和治疗性DNA疫苗。
Particle-mediated DNA delivery technologies (“gene guns”) have been shown in both animal and clinical studies to be an effective means of increasing the immunogenicity and protective efficacy of DNA vaccines. The primary goal in optimizing particle-mediated epidermal delivery (PMED) vaccination in different animal models is to achieve delivery of DNA-coated gold beads into the viable epidermis. Two key para-meters that influence this outcome include the delivery pressure, which controls the penetrative force of the beads into the skin, and the anatomical site of DNA delivery. Although the ferret has been extensively used as an experimental model for influenza infection in humans, very few studies have investigated the capacity for PMED DNA vaccination to induce protective immune responses in ferrets. Here we describe methods to optimize DNA vaccine delivery using the PowderJect XR1 gene delivery in ferrets. We first assess the effects of firing pressure on both the delivery of DNA-coated gold beads into the desired epidermal layer and the degree of DNA vaccine reporter gene expression at the target site. Second, we evaluate the impact of vaccination site (skin or tongue) on DNA vaccine immunogenicity by measuring serum antibody responses to the model antigens influenza virus hemagglutinin and hepatitis B core antigen. Results from these studies support the use of the PowderJect XR1 device in ferrets for the study of prophylactic and therapeutic DNA vaccines against clinically important diseases such as influenza virus infection.
DOI: 10.1016/s0264-410x(00)00302-9
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DOI: --
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