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The site of administration influences both the type and the magnitude of the immune response induced by DNA vaccine electroporation

机译:给药部位会影响DNA疫苗电穿孔诱导的免疫反应的类型和强度

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We investigated the influence of the site of administration of DNA vaccine on the induced immune response. DNA vaccines were administered by electroporation at three different sites: tibial cranial muscle, abdominal skin and ear pinna. Aiming to draw general conclusions about DNA vaccine delivery, we successively used several plasmids encoding either luciferase and ovalbumin as models or gp160 and PIA as vaccines against HIV and P815 mastocytoma, respectively. Low levels and duration of luciferase transgene expression were observed after electroporation of the abdominal skin, partly explaining its lower immunogenic performance as compared to the other sites of administration. Analyses of OT-I CD8+ and OT-II CD4+ T cell responses highlighted the differential impact of the delivery site on the elicited immune response. Muscle electroporation induced the strongest humoral immune response and both muscle and ear pinna sites induced cellular immunity against gp160. Ear pinna delivery generated the highest level of CTL responses against PIA but electrop oration of muscle and ear pinna were equally efficient in delaying P815 growth and improving mice survival. The present study demonstrated that the site of administration is a key factor to be tested in the development of DNA vaccine.(C) 2015 Elsevier Ltd. All rights reserved.
机译:我们调查了DNA疫苗给药部位对诱导的免疫反应的影响。 DNA疫苗是通过电穿孔在三个不同部位施用的:胫骨颅肌,腹部皮肤和耳廓。为了得出有关DNA疫苗递送的一般结论,我们先后使用了编码荧光素酶和卵清蛋白的几种质粒作为模型,或分别使用gp160和PIA作为抗HIV和P815肥大细胞瘤的疫苗。在腹部皮肤电穿孔后观察到萤光素酶转基因表达的水平低且持续时间长,部分解释了与其他给药部位相比其免疫原性较低。 OT-I CD8 +和OT-II CD4 + T细胞反应的分析突显了递送部位对引发的免疫反应的不同影响。肌肉电穿孔诱导最强的体液免疫反应,而肌肉和耳廓部位均诱导针对gp160的细胞免疫。耳廓递送对PIA产生最高水平的CTL反应,但是肌肉和耳廓的电穿孔术在延迟P815生长和改善小鼠存活方面同样有效。本研究表明,给药部位是DNA疫苗开发中要测试的关键因素。(C)2015 Elsevier Ltd.保留所有权利。

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