Tretyakova Irina, Tomai Mark, Vasilakos John, Pushko Peter
Medigen, Inc., Frederick, MD, United States.
3M Company, St. Paul, MN, United States.
Front Trop Dis. 2022 Mar;3. doi: 10.3389/fitd.2022.813671. Epub 2022 Mar 18.
Effective and simple delivery of DNA vaccines remains a key to successful clinical applications. Previously, we developed a novel class of DNA vaccines, sometimes called iDNA, which encodes the whole live-attenuated vaccine viruses. Compared to a standard DNA vaccine, an iDNA vaccine required a low dose to launch a live-attenuated vaccine or . The goal of this pilot study was to investigate if iDNA vaccine encoding live-attenuated Venezuelan equine encephalitis virus (VEEV) can be efficiently delivered by a microneedle device using a single-dose vaccination with naked iDNA plasmid. For this purpose, we used pMG4020 plasmid encoding live-attenuated V4020 vaccine of VEE virus. The V4020 virus contains structural gene rearrangement, as well as attenuating mutations genetically engineered to prevent reversion mutations. The pMG4020 was administered to experimental rabbits by using a hollow microstructured transdermal system (hMTS) microneedle device. No adverse events to vaccination were noted. Animals that received pMG4020 plasmid have successfully seroconverted, with high plaque reduction neutralization test (PRNT) antibody titers, similar to those observed in animals that received V4020 virus in place of the pMG4020 iDNA plasmid. We conclude that naked iDNA vaccine can be successfully delivered by using a single-dose vaccination with a microneedle device.
高效且简便地递送DNA疫苗仍然是临床应用成功的关键。此前，我们开发了一类新型DNA疫苗，有时称为iDNA，它编码整个减毒活疫苗病毒。与标准DNA疫苗相比，iDNA疫苗只需低剂量就能引发减毒活疫苗反应。本初步研究的目的是调查编码减毒委内瑞拉马脑炎病毒（VEEV）的iDNA疫苗能否通过微针装置使用裸iDNA质粒单剂量接种来有效递送。为此，我们使用了编码VEE病毒减毒V4020疫苗的pMG4020质粒。V4020病毒包含结构基因重排以及经过基因工程改造以防止回复突变的减毒突变。通过使用中空微结构透皮系统（hMTS）微针装置将pMG4020给予实验兔。未观察到接种的不良事件。接受pMG4020质粒的动物成功产生了血清转化，具有高蚀斑减少中和试验（PRNT）抗体滴度，类似于在接受V4020病毒而非pMG4020 iDNA质粒的动物中观察到的情况。我们得出结论，裸iDNA疫苗可以通过使用微针装置单剂量接种成功递送。
