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.
Public Health Relevance Statement: PROJECT NARRATIVE This project will develop a clinic ready, needle-free gene gun (termed the MACH-1) to deliver a room temperature stable universal influenza DNA vaccine. If successful, these studies will provide a high-performance clinic ready gene gun platform to deliver a universal influenza vaccine that could reduce the burden of influenza diseases worldwide and prevent the next influenza pandemic. These studies would also result in a needle-free, pain-free delivery device to efficiently deliver DNA and RNA vaccines for other infectious diseases and cancer.
Project Terms: Acceleration; Animals; Antibodies; Antibody Avidity; Antigenic Determinants; Binding Determinants; Epitopes; immunogen; Antigens; Malignant Neoplasms; Cancers; Malignant Tumor; malignancy; neoplasm/cancer; Cells; Cell Body; Communicable Diseases; Infectious Disease Pathway; Infectious Diseases; Infectious Disorder; Conserved Sequence; Cryopreservation; Cryofixation; cold preservation; cold storage; Disease; Disorder; DNA; Deoxyribonucleic Acid; Investigational Drugs; Investigational New Drugs; Engineering; Feedback; Future; Gases; Gold; Helium; He element; Housing; Human; Modern Man; Hydrogen; H element; Immunity; Influenza; Grippe; Lead; Pb element; heavy metal Pb; heavy metal lead; Manuals; Methods; Molecular Conformation; Molecular Configuration; Molecular Stereochemistry; conformation; conformational; conformational state; conformationally; conformations; Needles; Particle Size; Powder dose form; Powders; Power Sources; Power Supplies; pressure; RNA; Non-Polyadenylated RNA; RNA Gene Products; Ribonucleic Acid; Rodent; Rodentia; Rodents Mammals; Rotation; Safety; Standardization; Technology; Temperature; Testing; Time; Vaccines; Virus; Friends; Generations; human subject; improved; Area; Clinical; Penetration; Phase; Variation; Variant; Antigen Presentation; electroporative delivery; gene electrotransfer; Electroporation; non-painful; nonpainful; not painful; Painless; non-human primate; nonhuman primate; CD8 Cell; CD8 T cells; CD8 lymphocyte; CD8+ T cell; CD8+ T-Lymphocyte; CD8-Positive Lymphocytes; T8 Cells; T8 Lymphocytes; CD8-Positive T-Lymphocytes; Funding; Mucosal Immune Responses; Mucosal Immunity; Immunological response; host response; immune system response; immunoresponse; Immune response; Life; DNA Vaccines; Naked DNA Vaccines; Recombinant DNA Vaccines; Stream; Clinic; System; Viral; particle; Performance; Speed; Exclusion; Devices; portability; Pain Free; Documentation; Phase I Clinical Trials; Early-Stage Clinical Trials; Phase 1 Clinical Trials; phase I protocol; gene gun; Biolistics; Gene-Gun Technique; Skin; preventing; prevent; vaccine delivery; deliver vaccines; Address; Dose; Data; Dryness; Reproducibility; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Vaccine Design; transmission process; Transmission; Process; Modification; Development; developmental; pre-clinical; preclinical; flu virus pandemic; influenza virus pandemic; pandemic flu; pandemic strain of influenza; pandemic influenza; immunogenicity; flu serotype; flu strain; flu subtype; flu viral strain; flu virus strain; influenza serotype; influenza strain; influenza subtype; influenza viral strain; influenza virus strain; designing; design; manufacturing process; scale up; mucosal site; innovate; innovative; innovation; murine model; mouse model; deliver DNA; DNA delivery; protective efficacy; T cell response; phase 1 trial; phase I trial; Formulation; immune evasive; Immune Evasion; universal flu vaccine; universal influenza virus vaccine; universal vaccine against flu; universal vaccine against influenza; universal influenza vaccine; RNA-based vaccine; mRNA vaccine; mRNA-based vaccine; RNA vaccine; lipid based nanoparticle; lipid nanoparticle; clinical trial readiness; pig model; piglet model; swine model; porcine model; vaccine formulation; vaccine immunogenicity; vaccine immune response; future pandemic; next pandemic; pre-Investigational New Drug meeting; Pre IND FDA meeting; Pre-IND mtg; pre-IND consultation; pre-IND discussion; pre-IND meeting; clinic ready; clinical ready
