Optimizing particle-mediated epidermal delivery of an influenza DNA vaccine in ferrets

Particle-mediated DNA delivery technologies ("gene guns") have been shown in both animal and clinical studies to be an effective means of increasing the immunogenicity and protective efficacy of DNA vaccines. The primary goal in optimizing particle-mediated epidermal delivery (PMED) vaccination in different animal models is to achieve delivery of DNA-coated gold beads into the viable epidermis. Two key para-meters that influence this outcome include the delivery pressure, which controls the penetrative force of the beads into the skin, and the anatomical site of DNA delivery. Although the ferret has been extensively used as an experimental model for influenza infection in humans, very few studies have investigated the capacity for PMED DNA vaccination to induce protective immune responses in ferrets. Here we describe methods to optimize DNA vaccine delivery using the PowderJect XR1 gene delivery in ferrets. We first assess the effects of firing pressure on both the delivery of DNA-coated gold beads into the desired epidermal layer and the degree of DNA vaccine reporter gene expression at the target site. Second, we evaluate the impact of vaccination site (skin or tongue) on DNA vaccine immunogenicity by measuring serum antibody responses to the model antigens influenza virus hemagglutinin and hepatitis B core antigen. Results from these studies support the use of the PowderJect XR1 device in ferrets for the study of prophylactic and therapeutic DNA vaccines against clinically important diseases such as influenza virus infection.