Clinic-Ready MACH-1 Gene Gun for delivery of a universal influenza DNA vaccine

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PROJECT SUMMARY Orlance has developed a lead universal influenza (UFlu) DNA vaccine to address the need for a vaccine that can protect from annual influenza and the emergence of new variants that could cause future pandemics. Our UFlu vaccine is a multi-dose vaccine designed to induce systemic and mucosal immune responses that can prevent transmission and minimize disease from currently circulating and emerging strains by inducing broad antibody and cellular immune responses that target conserved viral sequences common across all influenza subtypes. Under previous SBIR funding, we showed that our gene gun (GG)-delivered UFlu DNA vaccine induced broadly specific (universal) antibody and T cell responses and protection from diverse influenza challenges in rodents and nonhuman primates. This vaccine is nearing Phase 1 human trials and will require a clinic ready GG device to administer it. Here, we propose to continue developing our promising MACH-1TM GG to deliver the lead UFlu DNA vaccine and other lead vaccines to humans. The MACH-1 is a needle-free device that delivers DNA- and/or RNA-coated gold microparticles directly into epidermal cells using high pressure gas. It is pain free, requires substantially lower doses of DNA or RNA to induce protective immunity compared to other delivery methods, and has been engineered with several innovations to maximize efficiency and reproducibility of delivery. Here, we will: improve the MACH-1 by making it portable and easier to use (Aim 1); develop a GMP- scalable DNA vaccine formulation into fill and finish disposable dosing units (Aim 2), and evaluate safety, immunogenicity, and efficacy of the UFlu vaccine delivered by the improved MACH-1 in mice and swine models (Aim 3). Successful completion of these Aims will result in Investigational New Drug (IND)-enabling documentation for the delivery system device and formulation platform necessary to advance our MACH-1 delivered UFlu DNA vaccine to Phase 1 trials.