Electroporation enhances protective immune response of a DNA vaccine against Japanese encephalitis in mice and pigs
Electroporation enhances protective immune response of a DNA vaccine against Japanese encephalitis in mice and pigs
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电穿孔增强 DNA 疫苗对小鼠和猪的日本脑炎保护性免疫反应
DOI：
10.1016/j.vaccine.2016.10.001
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发表时间：
2016-11-11
期刊：
影响因子：
5.5
通讯作者：
An, Jing
中科院分区：
文献类型：
--
作者：
Sheng, Ziyang;Gao, Na;An, Jing
日本脑炎病毒（JEV）是乙型脑炎（JE）的病原，乙型脑炎是一种由蚊子传播并经猪扩增的人畜共患疾病。乙脑病毒感染可导致严重的神经系统后遗症，甚至导致人类死亡和猪的生殖障碍。疫苗接种是控制人类乙脑病毒感染的唯一途径。鉴于猪在乙脑病毒传播周期中发挥着重要作用，开发新的兽用疫苗是切断乙脑病毒传播途径的有效策略。我们之前报道过表达乙脑病毒prM-E蛋白的DNA疫苗pCAG-JME通过肌肉注射在小鼠中有效。然而，由于免疫原的低表达，导致免疫原性差，这是阻碍DNA疫苗在大型动物中发展的主要障碍。因此，在本研究中，我们用pCAG-JME肌内免疫小鼠和猪，并伴有电穿孔（EP）刺激，这是一种有吸引力的基因传递方法。与IM相比，ep介导的疫苗接种显著增加了注射部位免疫原的表达，并诱导了剂量和时间依赖性的免疫反应。10 ~ 10014剂量组的存活率为100%，说明10 μ g的EP DNA足以对小鼠产生有效的保护作用。令人惊讶的是，即使DNA剂量较低（5 μ g），小鼠的抗乙脑病毒抗体的存活率和终点滴度也高于通过IM接种100 μ g的小鼠。值得注意的是，prM-E抗原在猪体内也引起了较高的抗体反应，中和抗体效价达到1:20 20。结果表明，至少在猪中，EP介导的DNA免疫可能是一种有效的预防乙脑病毒的策略，EP在DNA疫苗接种中具有潜在的应用前景。(C) 2016 Elsevier Ltd.版权所有。
Japanese encephalitis virus (JEV) is a pathogenic cause of Japanese Encephalitis (JE), which is a zoonotic disease transmitted by mosquitoes and amplified by pigs. Infection of JEV may lead to severe neurological sequelae, even death in humans and reproductive disorders in pigs. Vaccination is the only way to control JEV infection in humans. For pigs play important role in the JEV transmission cycle, developing a new veterinary vaccine is considered as a useful strategy for cutting off the transmission route of JEV. We have previously reported that DNA vaccine pCAG-JME, expressing prM-E proteins of JEV, is effective in mice through intramuscular injection (IM). However, the poor immunogenicity, due to low expression of immunogen, is the major obstacle for the development of DNA vaccine in large animals. In the present study, therefore, we immunized mice and pigs with pCAG-JME intramuscularly accompanied with electroporation (EP) stimulation, the attractive gene delivery approach. As compared with IM, EP-mediated vaccination markedly increased the expression of immunogen in the injection site and induced a dose and time-dependent immune response. 100% survival rate was observed in groups vaccinated with doses ranged from 10 to 10014, indicating that 10 mu g of DNA with EP for individual was enough for inducing effective protection in mice. Surprisingly, survival rate and end-point titers of anti-JEV antibodies were higher in mice even at lower dose of DNA (5 mu g) than that in mice inoculated 100 mu g through IM. Notably, the prM-E antigens also induced high antibody response in pig, while the neutralizing antibody titer achieved 1:320. Our results suggested that EP-mediated DNA immunization might act as an effective strategy against JEV, at least in pig, and that EP has a potential application prospect in DNA vaccination. (C) 2016 Elsevier Ltd. All rights reserved.