Integration of needle-free jet injection with advanced electroporation delivery enhances the magnitude, kinetics, and persistence of engineered DNA vaccine induced immune responses.
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.
['Jiang|Jingjing|J|', 'Ramos|Stephanie J|SJ|', 'Bangalore|Preeti|P|', 'Fisher|Paul|P|', 'Germar|Kristine|K|', 'Lee|Brian K|BK|', 'Williamson|Dan|D|', 'Kemme|Andrea|A|', 'Schade|Eric|E|', 'McCoy|Jay|J|', 'Muthumani|Kar|K|', 'Weiner|David B|DB|', 'Humeau|Laurent M|LM|', 'Broderick|Kate E|KE|']
D000818:Animals D000914:Antibodies, Viral D018274:Electroporation D005260:Female D007111:Immunity, Cellular D056724:Immunity, Humoral D000071497:Immunogenicity, Vaccine D007271:Injections, Intradermal D007277:Injections, Jet D007700:Kinetics D008297:Male D011323:Primates D000075082:Proof of Concept Study D011817:Rabbits D014611:Vaccination D019444:Vaccines, DNA
Electroporation DNA vaccine Immunogenicity Needle-free injection