用于生物防御应用的DNA启动的减毒活疫苗。
DNA-launched live-attenuated vaccines for biodefense applications.
作者信息
Pushko Peter, Lukashevich Igor S, Weaver Scott C, Tretyakova Irina
机构信息
a Medigen, Inc ., Frederick , MD , USA.
b Department of Pharmacology and Toxicology, School of Medicine, Center for Predictive Medicine and Emerging Infectious Diseases , University of Louisville , Louisville , KY , USA.
出版信息
Expert Rev Vaccines. 2016 Sep;15(9):1223-34. doi: 10.1080/14760584.2016.1175943. Epub 2016 Apr 25.
A novel vaccine platform uses DNA immunization to launch live-attenuated virus vaccines in vivo. This technology has been applied for vaccine development against positive-strand RNA viruses with global public health impact including alphaviruses and flaviviruses. The DNA-launched vaccine represents the recombinant plasmid that encodes the full-length genomic RNA of live-attenuated virus downstream from a eukaryotic promoter. When administered in vivo, the genomic RNA of live-attenuated virus is transcribed. The RNA initiates limited replication of a genetically defined, live-attenuated vaccine virus in the tissues of the vaccine recipient, thereby inducing a protective immune response. This platform combines the strengths of reverse genetics, DNA immunization and the advantages of live-attenuated vaccines, resulting in a reduced chance of genetic reversions, increased safety, and improved immunization. With this vaccine technology, the field of DNA vaccines is expanded from those that express subunit antigens to include a novel type of DNA vaccines that launch live-attenuated viruses.
一种新型疫苗平台利用DNA免疫在体内启动减毒活病毒疫苗。这项技术已应用于针对对全球公共卫生有影响的正链RNA病毒（包括甲病毒和黄病毒）的疫苗开发。DNA启动疫苗是指在真核启动子下游编码减毒活病毒全长基因组RNA的重组质粒。当在体内给药时，减毒活病毒的基因组RNA会被转录。该RNA在疫苗接种者的组织中引发基因定义的减毒活疫苗病毒的有限复制，从而诱导保护性免疫反应。这个平台结合了反向遗传学、DNA免疫的优势以及减毒活疫苗的优点，降低了基因回复突变的几率，提高了安全性，并改善了免疫效果。借助这种疫苗技术，DNA疫苗领域从表达亚单位抗原的疫苗扩展到包括一种新型的启动减毒活病毒的DNA疫苗。
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