Optimization of Electroporation-Enhanced Intradermal Delivery of DNA Vaccine Using a Minimally Invasive Surface Device
Optimization of Electroporation-Enhanced Intradermal Delivery of DNA Vaccine Using a Minimally Invasive Surface Device
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DOI：
10.1089/hgtb.2011.209
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发表时间：
2012-06-01
影响因子：
--
通讯作者：
Sardesai, Niranjan Y.
中科院分区：
文献类型：
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作者：
Lin, Feng;Shen, Xuefei;Sardesai, Niranjan Y.
体内电穿孔 (EP) 是一种有效的非病毒方法，可增强动物和人类的 DNA 疫苗递送和免疫原性。由于皮肤组织的免疫能力，DNA 疫苗的皮内递送是一种有吸引力的策略。我们之前报道过一种用于输送预防性 DNA 疫苗的微创表面皮内 EP (SEP) 装置。在几种测试的动物模型中，通过表面 EP 注射疫苗后，诱导了强烈的抗体反应。在这里，我们进一步研究了有效递送 DNA 疫苗的最佳 EP 参数，特别强调除了强大的体液反应之外还引发细胞免疫。在小鼠模型中，使用 10-100 V 的外加电压，与仅注射 DNA 相比，当使用低至 10 V 的电压时，绿色荧光蛋白和荧光素酶报告基因的转基因表达显着增加。当施加 20 V 或更低的电压时，无法检测到皮肤组织损伤。然而，在高于 40 V 的电压下，炎症和瘀伤变得明显。在 10-100V 的施加电压下输送编码流感病毒 H5 血凝素 (H5HA) 和 H1N1 流感核蛋白 (NP) 的 DNA 疫苗，引发了强烈且持续的抗体反应。此外，两次免疫后，与高电压（高于20 V）EP组相比，低电压（低于20 V）EP组引发了更高、更持续的细胞免疫反应。数据证实，使用 SEP 装置的低压 EP 能够有效地将 DNA 疫苗输送到皮肤中，并确定这些参数足以引发强大且可持续的体液和细胞免疫反应，而不会损伤组织。在这些参数范围内发挥作用的 SEP 装置可能具有重要的临床应用，可用于针对 HIV 感染、疟疾和结核病等需要细胞和体液免疫反应进行保护的疾病提供预防性 DNA 疫苗。
In vivo electroporation (EP) is an efficient nonviral method for enhancing DNA vaccine delivery and immunogenicity in animals and humans. Intradermal delivery of DNA vaccines is an attractive strategy because of the immunocompetence of skin tissue. We have previously reported a minimally invasive surface intradermal EP (SEP) device for delivery of prophylactic DNA vaccines. Robust antibody responses were induced after vaccine delivery via surface EP in several tested animal models. Here we further investigated the optimal EP parameters for efficient delivery of DNA vaccines, with a specific emphasis on eliciting cellular immunity in addition to robust humoral responses. In a mouse model, using applied voltages of 10-100 V, transgene expression of green fluorescent protein and luciferase reporter genes increased significantly when voltages as low as 10 V were used as compared with DNA injection only. Tissue damage to skin was undetectable when voltages of 20 V and less were applied. However, inflammation and bruising became apparent at voltages above 40 V. Delivery of DNA vaccines encoding influenza virus H5 hemagglutinin (H5HA) and nucleoprotein (NP) of influenza H1N1 at applied voltages of 10-100V elicited robust and sustained antibody responses. In addition, low-voltage (less than 20 V) EP elicited higher and more sustained cellular immune responses when compared with the higher voltage (above 20 V) EP groups after two immunizations. The data confirm that low-voltage EP, using the SEP device, is capable of efficient delivery of DNA vaccines into the skin, and establishes that these parameters are sufficient to elicit both robust and sustainable humoral as well as cellular immune responses without tissue damage. The SEP device, functioning within these parameters, may have important clinical applications for delivery of prophylactic DNA vaccines against diseases such as HIV infection, malaria, and tuberculosis that require both cellular and humoral immune responses for protection.