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

Document text

Principal Investigator: Kenneth C Bagley
Organization: ORLANCE, INC.
Fiscal Year: 2023
Award: $996,500
Funding agency: National Institute of Allergy and Infectious Diseases

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.

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