Enhanced immunogenicity and protective efficacy of a tetravalent dengue DNA vaccine using electroporation and intradermal delivery

Tetravalent dengue DNA vaccine is not immunogenic when delivered by retrograde infusion into salivary glands

“…While the method of parotid gland infusion was simple and reproducible and resulted in no complications with the subject animals, infusion of the plasmid vaccine did not elicit an appreciable immune response. These findings appeared at odds with the sizable titers reported by Tucker et al in response to DNA vaccine delivery into the salivary glands of rodents and dogs [8,9] Given the better immunologic responses to this vaccine reported using standard techniques in this model [6] and the exploratory nature of this approach, it was important to confirm that the infusion technique was adequate to deliver the vaccine to the target tissue. We repeated the procedure under fluoroscopic imaging and demonstrated that a similar volume, fluid bolus was appropriately distributed throughout the gland, confirming the validity of the delivery technique.…”

“…Vaccines and vaccine candidates that elicit sub-optimal immune responses are natural test candidates for these types of approaches and technologies. For example, a recent study that assessed utilizing electroporation to administer TVDV showed encouraging results [6]. Infusion of plasmid DNA into the salivary gland has been reported to elicit a robust immune response in both rats and dogs [8,9].…”

“…A tetravalent DNA vaccine for Dengue virus (TVDV) is under development but has not yet achieved optimal immunogenicity [5]. Alternative administration methods have recently shown promise in boosting the vaccine's immunogenicity, but further increasing immunogenicity would aid in the vaccine's development [6]. One lesser-known DNA vaccine administration site reported to result in high titer responses in rodents and dogs is the salivary gland [7][8][9].…”

“…For the third infusion (day 98), in an effort to increase transfection into salivary tissue, two animals received 100ul TVDV mixed with 400ul polyethylenamine (PEI) 1μg/ml for total volume of 500ul/gland; and the other two macaques were infused with 500ul/gland TVDV solution with zinc. Serial antibody titers were obtained 4 weeks following second and third infusion as previously described [6]. Thereafter, we went on to test whether or not the procedure resulted in delivery of the infusate into the gland as planned; and whether or not transfection of the infused DNA occurred in the salivary gland cells.…”

Induction of a local muscular dystrophy using electroporation in vivo: an easy tool for screening therapeutics

“…high intrinsic toxicity but low plasma membrane permeability [12][13][14] . Besides its direct clinical application in the field of cancer, EP is broadly used as a gene delivery tool 15 that can be applied either for vaccination [16][17][18][19][20] , immunotherapy (especially in cancer applications 21,22 ), gene therapy [23][24][25][26] , genome editing 27,28 and generation of induced pluripotent stem cells 29,30 . Number of phase I and II clinical trials are underway or have been completed, demonstrating the safety and efficacy of this procedure 3 .…”