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皮内电穿孔递送炭疽 DNA 疫苗的免疫原性和生物分布。

Immunogenicity and Biodistribution of Anthrax DNA Vaccine Delivered by Intradermal Electroporation.

机构信息

ABION Inc., R&D Center, Seoul, Korea.

The 4th R & D Institute Directorate, Agency for Defense Development, Daejon, Korea.

出版信息

Curr Drug Deliv. 2020;17(5):414-421. doi: 10.2174/1567201817666200414144550.

Abstract

PURPOSE

Anthrax is a lethal bacterial disease caused by gram-positive bacterium Bacillus anthracis and vaccination is a desirable method to prevent anthrax infections. In the present study, DNA vaccine encoding a protective antigen of Bacillus anthracis was prepared and we investigated the influence of DNA electrotransfer in the skin on the induced immune response and biodistribution.

METHODS AND RESULTS

The tdTomato reporter gene for the whole animal in vivo imaging was used to assess gene transfer efficiency into the skin as a function of electrical parameters. Compared to that with 25 V, the transgene expression of red fluorescent protein increased significantly when a voltage of 90 V was used. Delivery of DNA vaccines expressing Bacillus anthracis protective antigen domain 4 (PAD4) with an applied voltage of 90 V induced robust PA-D4-specific antibody responses. In addition, the in vivo fate of anthrax DNA vaccine was studied after intradermal administration into the mouse. DNA plasmids remained at the skin injection site for an appropriate period of time after immunization. Intradermal administration of DNA vaccine resulted in detection in various organs (viz., lung, heart, kidney, spleen, brain, and liver), although the levels were significantly reduced.

CONCLUSION

Our results offer important insights into how anthrax DNA vaccine delivery by intradermal electroporation affects the immune response and biodistribution of DNA vaccine. Therefore, it may provide valuable information for the development of effective DNA vaccines against anthrax infection.

摘要

目的

炭疽是一种由革兰氏阳性细菌炭疽芽孢杆菌引起的致命细菌性疾病,接种疫苗是预防炭疽感染的理想方法。在本研究中,我们制备了编码炭疽芽孢杆菌保护性抗原的 DNA 疫苗,并研究了 DNA 电转移对皮肤诱导免疫应答和生物分布的影响。

方法和结果

使用 tdTomato 报告基因对整个动物进行体内成像,以评估电参数对皮肤中转基因表达的影响。与 25 V 相比,当使用 90 V 电压时,红色荧光蛋白的转基因表达显著增加。用 90 V 施加电压递送表达炭疽芽孢杆菌保护性抗原结构域 4(PAD4)的 DNA 疫苗可诱导强烈的 PA-D4 特异性抗体应答。此外,在将炭疽 DNA 疫苗皮内给药后,研究了其体内命运。在免疫后,DNA 质粒在皮肤注射部位保持适当的一段时间。DNA 疫苗的皮内给药导致在各种器官(即肺、心脏、肾脏、脾脏、大脑和肝脏)中检测到,但水平显著降低。

结论

我们的结果提供了有关炭疽 DNA 疫苗通过皮内电穿孔递送如何影响 DNA 疫苗的免疫应答和生物分布的重要见解。因此,它可能为开发针对炭疽感染的有效 DNA 疫苗提供有价值的信息。

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