Suschak John J, Bixler Sandra L, Badger Catherine V, Spik Kristin W, Kwilas Steven A, Rossi Franco D, Twenhafel Nancy, Adams Melissa L, Shoemaker Charles J, Spiegel Erin, Hooper Jay W
U.S. Army Medical Research Institute of Infectious Diseases, 1425 Porter St, Fort Detrick, MD, 21702, USA.
PharmaJet, Inc., 400 Corporate Circle, Suite N, Golden, CO, 80401, USA.
NPJ Vaccines. 2022 Apr 22;7(1):46. doi: 10.1038/s41541-022-00469-x.
We have previously shown that DNA vaccines expressing codon optimized alphavirus envelope glycoprotein genes protect both mice and nonhuman primates from viral challenge when delivered by particle-mediated epidermal delivery (PMED) or intramuscular (IM) electroporation (EP). Another technology with fewer logistical drawbacks is disposable syringe jet injection (DSJI) devices developed by PharmaJet, Inc. These needle-free jet injection systems are spring-powered and capable of delivering vaccines either IM or into the dermis (ID). Here, we evaluated the immunogenicity of our Venezuelan equine encephalitis virus (VEEV) DNA vaccine delivered by either the IM- or ID-DSJI devices in nonhuman primates. The protective efficacy was assessed following aerosol challenge. We found that a prime and single boost by either the IM or ID route resulted in humoral and cellular immune responses that provided significant protection against disease and viremia. Although the ID route utilized one-fifth the DNA dose used in the IM route of vaccination, and the measured humoral and cellular immune responses trended lower, the level of protection was high and performed as well as the IM route for several clinical endpoints.
我们之前已经表明,通过颗粒介导的表皮递送(PMED)或肌肉内(IM)电穿孔(EP)递送时,表达密码子优化的甲病毒包膜糖蛋白基因的DNA疫苗可保护小鼠和非人类灵长类动物免受病毒攻击。另一种后勤缺点较少的技术是由PharmaJet公司开发的一次性注射器喷射注射(DSJI)设备。这些无针喷射注射系统由弹簧驱动,能够将疫苗肌肉内注射或真皮内注射(ID)。在这里,我们评估了通过IM或ID-DSJI设备在非人类灵长类动物中递送的委内瑞拉马脑炎病毒(VEEV)DNA疫苗的免疫原性。在气溶胶攻击后评估保护效力。我们发现,通过IM或ID途径进行初次免疫和单次加强免疫会产生体液和细胞免疫反应,从而为疾病和病毒血症提供显著保护。尽管ID途径使用的DNA剂量是IM疫苗接种途径的五分之一,并且测得的体液和细胞免疫反应趋势较低,但保护水平很高,并且在几个临床终点上的表现与IM途径相同。