Integration of needle-free jet injection with advanced electroporation delivery enhances the magnitude, kinetics, and persistence of engineered DNA vaccine induced immune responses. Issue 29 (27th June 2019)

• Record Type: Journal Article
• Authors: Jiang, Jingjing; Ramos, Stephanie J.; Bangalore, Preeti; Fisher, Paul; Germar, Kristine; Lee, Brian K.; Williamson, Dan; Kemme, Andrea; Schade, Eric; McCoy, Jay; Muthumani, Kar; Weiner, David B.; Humeau, Laurent M.; Broderick, Kate E.
• Is Part Of: Vaccine. Volume 37:Issue 29(2019)
• Page Start: 3832
• Page End: 3839
• Publication Date: 2019-06-27
• Subjects: DNA vaccine -- Needle-free injection -- Electroporation -- Immunogenicity; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2019.05.054
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: Electroporation enhances DNA muscle transfection over needle-free jet injection. Adding EP to Jet delivery improves DNA vaccine induced immune responses in NHPs. Enhanced antibody levels sustained at least 9 months post Jet-EP delivery in NHPs. Abstract: The combination of optimized DNA constructs, improved formulations and advanced in vivo electroporation (EP) has been shown to generate potent and efficacious immune responses in the clinic. Needle-free jet injection has also been reported to improve DNA vaccine delivery over standard needle and syringe in clinical trials. Here we investigated the impact of combined jet injection and EP (Jet-EP) delivery on muscle transfection efficiency and DNA vaccine immunogenicity in rabbits and nonhuman primates (NHPs) compared to jet injection alone. Our results show that the addition of EP significantly enhanced in vivo DNA transfection efficiency of rabbit muscle over jet injection alone. Jet-EP delivery augmented the rate and magnitude of DNA vaccine induced humoral and cellular responses over jet injection alone in both rabbits and NHPs. Jet-EP delivery also resulted in higher proportions of polyfunctional antigen specific T cells producing IFNγ, IL-2, and/or TNFα. Elevated antibody levels were sustained nine months post immunization in NHPs immunized with a DNA vaccine using Jet-EP delivery, far outperforming jet delivery alone. Our results provide proof-of-concept that addition of advanced EP to needle-free jet injection delivery improves in vivo DNA transfection efficiency, increasing the magnitude, rate and duration of cellular and humoral immune responses to DNA vaccines. This combination likely has significant advantages in important vaccine and immunotherapy settings.