Suschak John J, Dupuy Lesley C, Shoemaker Charles J, Six Carolyn, Kwilas Steven A, Spik Kristin W, Williams James A, Schmaljohn Connie S
Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21702, USA.
Mol Ther Methods Clin Dev. 2020 Apr 15;17:810-821. doi: 10.1016/j.omtm.2020.04.009. eCollection 2020 Jun 12.
DNA vaccines expressing codon-optimized Venezuelan equine encephalitis virus (VEEV) and Ebola virus (EBOV) glycoprotein genes provide protective immunity to mice and nonhuman primates when delivered by intramuscular (IM) electroporation (EP). To achieve equivalent protective efficacy in the absence of EP, we evaluated VEEV and EBOV DNA vaccines constructed using minimalized Nanoplasmid expression vectors that are smaller than conventional plasmids used for DNA vaccination. These vectors may also be designed to co-express type I interferon inducing innate immune agonist genes that have an adjuvant effect. Nanoplasmid vaccinated mice had increased antibody responses as compared to those receiving our conventional pWRG7077-based vaccines when delivered by IM injection, and these responses were further enhanced by the inclusion of the innate immune agonist genes. The Nanoplasmid VEEV DNA vaccines also significantly increased protection against aerosol VEEV challenge as compared to the pWRG7077 VEEV DNA vaccine. Although all mice receiving the pWRG7077 and Nanoplasmid EBOV DNA vaccines at the dose tested survived EBOV challenge, only mice receiving the Nanoplasmid EBOV DNA vaccine that co-expresses the innate immune agonist genes failed to lose weight after challenge. Our results suggest that Nanoplasmid vectors can improve the immunogenicity and protective efficacy of alphavirus and filovirus DNA vaccines.
表达密码子优化的委内瑞拉马脑炎病毒（VEEV）和埃博拉病毒（EBOV）糖蛋白基因的DNA疫苗，通过肌肉内（IM）电穿孔（EP）给药时，可为小鼠和非人灵长类动物提供保护性免疫。为了在不进行EP的情况下实现等效的保护效果，我们评估了使用比用于DNA疫苗接种的传统质粒更小的最小化纳米质粒表达载体构建的VEEV和EBOV DNA疫苗。这些载体还可设计为共表达具有佐剂作用的I型干扰素诱导先天免疫激动剂基因。与通过IM注射接受我们基于传统pWRG7077的疫苗的小鼠相比，接种纳米质粒的小鼠抗体反应有所增加，并且通过包含先天免疫激动剂基因，这些反应进一步增强。与pWRG7077 VEEV DNA疫苗相比，纳米质粒VEEV DNA疫苗对气溶胶VEEV攻击的保护作用也显著增强。尽管所有以测试剂量接受pWRG7077和纳米质粒EBOV DNA疫苗的小鼠在EBOV攻击后均存活，但只有接受共表达先天免疫激动剂基因的纳米质粒EBOV DNA疫苗的小鼠在攻击后体重未减轻。我们的结果表明，纳米质粒载体可以提高甲病毒和丝状病毒DNA疫苗的免疫原性和保护效果。
