A novel prototype device for electroporation-enhanced DNA vaccine delivery simultaneously to both skin and muscle
A novel prototype device for electroporation-enhanced DNA vaccine delivery simultaneously to both skin and muscle
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DOI：
10.1016/j.vaccine.2010.12.057
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发表时间：
2011-09-09
期刊：
影响因子：
5.5
通讯作者：
Sardesai, Niranjan Y.
中科院分区：
文献类型：
--
作者：
Lin, Feng;Shen, Xuefei;Sardesai, Niranjan Y.
肌肉或皮肤的电穿孔（EP）已被证明是一种有效的方法，用于增加基于DNA的疫苗在小型和大型动物中的递送和免疫原性。先前在大型动物中的比较研究表明，肌内（i.m.）DNA EP递送似乎有利于细胞免疫，而皮内（i.d.）EP递送可能有利于体液免疫。虽然目前的EP设备主要设计用于i.m.或I.D.递送，我们开发了一种用于EP介导的同时i.d.和i.m.递送基于DNA的疫苗，试图引发上级抗体和细胞免疫应答。我们比较了DDD EP输送与标准i.d. EP，标准i.m. EP和i.d.和i.m. EP在不同的位点，诱导抗原特异性免疫应答的能力。在使用编码流感病毒H5血凝素（H5HA）的SynCon（TM）DNA疫苗的豚鼠模型中，通过DDD或联合递送的疫苗接种诱导的抗体滴度高于通过id.或i.m.单独送货。在使用编码H1N1流感核蛋白（NP）的DNA疫苗的小鼠模型中，产生的抗体应答趋势与豚鼠研究中检测到的相似。重要的是，DDD或联合给药组的细胞免疫应答显著强于id.或i.m.。交付组。我们的结论是，EP介导的DNA为基础的疫苗输送到皮肤和肌肉是上级交付到任何组织单独诱导抗原特异性抗体和细胞免疫。(C)2011爱思唯尔有限公司保留所有权利。
Electroporation (EP) of either muscle or skin has proven to be an efficient method for increasing DNA-based vaccine delivery and immunogenicity in small and large animals. Previous comparative studies in large animals suggest that intramuscular (i.m.) DNA EP delivery appears to favor cellular immunity, while intradermal (i.d.) EP delivery may favor humoral immunity. While current EP devices are primarily designed either for i.m. or i.d. delivery, we developed a novel prototype Dual-Depth Device (DDD) for EP-mediated simultaneous i.d. and i.m. delivery of DNA-based vaccines with an attempt to elicit superior antibody and cellular immune responses. We performed comparisons of DDD EP delivery with standard i.d. EP, standard i.m. EP, and combined delivery of i.d. and i.m. EP at separate sites, for the ability to induce antigen-specific immune responses. In a guinea pig model using a SynCon (TM) DNA vaccine encoding the influenza virus H5 hemaglutinin (H5HA), vaccination via DDD or combined delivery induced higher antibody titers than via either id. or i.m. delivery alone. In a mouse model using a DNA vaccine encoding the nucleoprotein (NP) of influenza H1N1, the resulting trend of antibody responses was similar to that detected in guinea pig study. Importantly, cellular immune responses in the DDD or combined delivery groups were significantly stronger than that in either id. or i.m. delivery groups. We conclude that EP-mediated DNA-based vaccine delivery to both skin and muscle is superior to delivery to either tissue alone for induction of antigen-specific antibody and cellular immunity. (C) 2011 Elsevier Ltd. All rights reserved.