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低电压电穿孔可使DNA疫苗为小鼠提供针对致死性H5N1禽流感病毒攻击的保护。

Electroporation at low voltages enables DNA vaccine to provide protection against a lethal H5N1 avian influenza virus challenge in mice.

作者信息

Zhou Yu, Fang Fang, Chen Jianjun, Wang Huadong, Chang Haiyan, Yang Zhongdong, Chen Ze

机构信息

College of Life Sciences, Hunan Normal University, Changsha, China.

出版信息

Intervirology. 2008;51(4):241-6. doi: 10.1159/000156483. Epub 2008 Sep 24.

Abstract

OBJECTIVE

Electroporation has been proved to enhance the efficacy of intramuscular delivery of DNA. However, the process of electroporation causes pain and discomfort to the patient receiving the treatment. Higher the electroporation voltages inflict greater pain, and this limits the circumstances in which the technique can be used clinically. The voltages generally used for electroporation in animals range from 100 to 1,200 V/cm. We studied the effect of DNA vaccination when electroporation was performed at lower voltages.

METHODS

BALB/c mice were immunized twice by electroporation, at a 3-week interval, with H5N1 virus hemagglutinin (HA) DNA. One week after the booster had been given, the mice were challenged with a lethal dose of mouse-adapted H5N1 virus. The immune effects of HA DNA were evaluated by the survival rate, lung virus titer, bodyweight change and antibody titer of the mice.

RESULTS

The higher the voltage used, the more able were the mice to survive the challenge. However, a significant degree of protection could also be achieved with a voltage as low as 5 V. When electroporation was performed at a voltage of 10 V, an immunization amount of 5 microg is enough for HA DNA to provide effective protection.

CONCLUSION

Low-voltage electroporation can induce immunity and protect mice effectively. There is, therefore, the potential to reduce the voltages currently used for DNA electroporation.

摘要

目的

电穿孔已被证明可提高肌肉注射DNA的效果。然而,电穿孔过程会给接受治疗的患者带来疼痛和不适。电穿孔电压越高,疼痛越剧烈,这限制了该技术在临床中的应用情况。动物电穿孔通常使用的电压范围为100至1200 V/cm。我们研究了在较低电压下进行电穿孔时DNA疫苗接种的效果。

方法

用H5N1病毒血凝素(HA)DNA对BALB/c小鼠进行两次电穿孔免疫,间隔3周。在给予加强免疫一周后,用致死剂量的鼠适应H5N1病毒攻击小鼠。通过小鼠的存活率、肺病毒滴度、体重变化和抗体滴度评估HA DNA的免疫效果。

结果

使用的电压越高,小鼠在攻击中存活的能力越强。然而,低至5 V的电压也能实现显著程度的保护。当以10 V的电压进行电穿孔时,5μg的免疫剂量足以使HA DNA提供有效的保护。

结论

低电压电穿孔可有效诱导免疫并保护小鼠。因此,有降低目前用于DNA电穿孔的电压的潜力。

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