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用于肾综合征出血热的DNA疫苗:实验室和临床研究

DNA vaccines for HFRS: laboratory and clinical studies.

作者信息

Schmaljohn Connie S, Spik Kristin W, Hooper Jay W

机构信息

U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.

U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.

出版信息

Virus Res. 2014 Jul 17;187:91-6. doi: 10.1016/j.virusres.2013.12.020. Epub 2013 Dec 24.

Abstract

DNA vaccines can be constructed to produce specific immunogens while avoiding the risks associated with propagating infectious viruses. Plasmid DNA vaccines have well established manufacturing procedures and are safe in that they are replication defective, cannot revert to virulence and cannot be transmitted from person-to-person or into the environment. In addition, DNA vaccines can be combined to form multivalent formulations and can be delivered by a variety of methods. Because of these numerous advantages, we have developed DNA vaccines expressing the envelope glycoprotein genes of hantaviruses causing hemorrhagic fever with renal syndrome (HFRS). We have demonstrated that these DNA vaccines elicit neutralizing antibodies in multiple laboratory animal species when delivered to skin or muscle tissues. Moreover, these vaccines delivered as active vaccines or passive vaccines (e.g., transfer of sera from vaccinated rabbits or nonhuman primates), protected hamsters from infection with HFRS-causing hantaviruses. Early clinical studies of HFRS vaccines expressing Hantaan virus or Puumala virus genes have been completed and show promise for further development. Despite these advantages, issues relating to inconsistent immunogenicity and immune interference remain to be addressed.

摘要

可以构建DNA疫苗来产生特定的免疫原,同时避免与传播传染性病毒相关的风险。质粒DNA疫苗具有成熟的生产程序,并且是安全的,因为它们复制有缺陷,不能恢复毒力,也不能在人与人之间传播或传播到环境中。此外,DNA疫苗可以组合形成多价制剂,并可以通过多种方法递送。由于这些众多优点,我们开发了表达引起肾综合征出血热(HFRS)的汉坦病毒包膜糖蛋白基因的DNA疫苗。我们已经证明,当将这些DNA疫苗递送至皮肤或肌肉组织时,它们会在多种实验动物物种中引发中和抗体。此外,作为主动疫苗或被动疫苗递送的这些疫苗(例如,从接种疫苗的兔子或非人类灵长类动物转移血清)可保护仓鼠免受引起HFRS的汉坦病毒感染。表达汉滩病毒或普马拉病毒基因的HFRS疫苗的早期临床研究已经完成,并显示出进一步开发的前景。尽管有这些优点,但与免疫原性不一致和免疫干扰相关的问题仍有待解决。

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