The relative immunogenicity of DNA vaccines delivered by the intramuscular needle injection, electroporation and gene gun methods

The relative immunogenicity of DNA vaccines delivered by the intramuscular needle injection, electroporation and gene gun methods
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肌内注射、电穿孔和基因枪方法递送DNA疫苗的相对免疫原性

DOI:
10.1016/j.vaccine.2008.02.033
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发表时间:
2008-04-16
期刊:
影响因子:
5.5
通讯作者:
Lu, Shan
Lu, Shan
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Shixia;Zhang, Chunghua;Lu, Shan

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DNA疫苗的免疫原性由于许多因素而显著变化,包括DNA疫苗中编码的蛋白质抗原的固有免疫原性,最佳免疫原性。可以在不同动物中实现免疫应答。模型和具有不同遗传背景的人类,以及在很大程度上用于施用DNA疫苗的递送方法。根据已发表的结果,只有基因枪介导的递送方法能够仅通过DNA免疫在健康成年志愿者中引起保护水平的免疫反应,而无需使用另一种疫苗形式作为加强。动物的最新结果研究表明电穿孔在引发高水平免疫应答中也是有效的。然而,目前还没有报道确定这两种主要的针对传染病靶标的DNA疫苗物理递送方法之间的相似性和差异。在本研究中,我们比较了表达来自H5 N1流感病毒的血凝素(HA)抗原的DNA疫苗在两种动物模型(兔和小鼠)中的相对免疫原性,当通过肌肉注射免疫(IM)、基因枪(GG)或电穿孔(EP)递送时。分析HA特异性抗体、T细胞和B细胞应答。我们的结果表明,总体而言,GG和EP方法比IM方法更具免疫原性。而EP和IM则刺激Th-1型抗体应答,而对GG的抗体应答则以Th-2为主。这些发现为进一步选择和优化用于人类应用的DNA疫苗递送方法提供了重要信息。(C)2008爱思唯尔有限公司保留所有权利。
Immunogenicity of DNA vaccines varies significantly due to many factors including the inherent immunogenicity of the protein antigen encoded in the DNA vaccine, the optimal. immune responses that can be achieved in different animal. models and in humans with different genetic backgrounds and, to a great degree, the delivery methods used to administer the DNA vaccines. Based on published results, only the gene gun-mediated delivery approach has been able to elicit protective levels of immune responses in healthy, adult volunteers by DNA immunization alone without the use of another vaccine modality as a boost. Recent results from animal. studies suggest that electroporation is also effective in eliciting high level immune responses. However, there have been no reports to identify the similarities and differences between these two leading physical delivery methods for DNA vaccines against infectious disease targets. In the current study, we compared the relative immunogenicity of a DNA vaccine expressing a hemagglutinin (HA) antigen from an H5N1 influenza virus in two animal models (rabbit and mouse) when delivered by either intramuscular needle immunization (IM), gene gun (GG) or electroporation (EP). HA-specific antibody, T cell and B cell responses were analyzed. Our results indicate that, overall, both the GG and EP methods are more immunogenic than the IM method. However, EP and IM stimulated a Th-1 type antibody response and the antibody response to GG was Th-2 dominated. These findings provide important information for the further selection and optimization of DNA vaccine delivery methods for human applications. (C) 2008 Elsevier Ltd. All rights reserved.