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Principal Investigator: Hannah Frizzell
Organization: ORLANCE, INC.
Fiscal Year: 2024
Award: $300,000
Funding agency: National Institute of Allergy and Infectious Diseases
PROJECT SUMMARY
COVID-19 launched mRNA vaccines to the forefront as the most effective and rapid strategy to respond to the
pandemic. mRNA vaccines require formulation in lipid nanoparticles (LNPs) to protect the mRNA from
degradation and to achieve efficient intracellular delivery. However, LNP-mRNA vaccines pose a real risk of
causing transient myocarditis and a requirement for ultra-cold storage to maintain stability. Gene gun (GG)
delivery holds considerable potential to improve the safety and stability of RNA vaccines. GG delivery results in
the direct microinjection of DNA and/or RNA vaccine-coated gold microparticles into cells of the epidermis.
Delivery into the highly immunocompetent skin layer, including direct transfection of local antigen presenting
cells, results in robust immunogenicity with very low doses of DNA or RNA. In addition, the dry, nuclease-free
formulation holds potential to offer stable ambient formulation that could obviate the need for ultra-cold storage.
GG delivery to the epidermis is also needle-free and pain-free and eliminates the need for LNP formulation that
may contribute to the rare adverse events, including myocarditis associated with mRNA/LNP vaccines.
Furthermore, GG delivery into the skin, in contrast to the muscle, elicits robust mucosal antibody and T cell
responses that could enhance protection from mucosally transmitted diseases. In the 1990s, PowderJect
Vaccines developed a prototype clinical GG that showed, for first time, the ability of a DNA vaccine to induce
protective levels of immunity in humans. Orlance has since implemented engineering improvements to this
device resulting in enhanced dose delivery, immunogenicity, and field-/clinic-friendly features such as battery
power, automatic dose advancement, and lock-out functions. Historically, the GG delivered only DNA vaccines
but due to its physical mechanism of intracellular delivery, we have found that GG can also efficiently deliver
RNA vaccines in a dry formulation that could offer significant advantages in warmer temperature stability, efficacy
at lower doses, and improved safety/reactogenicity. Indeed, our preliminary studies show that the GG can
effectively deliver RNA vaccines and GG delivery of low doses of RNA induces comparable immunogenicity as
RNA vaccines delivered in LNPs. In Phase I SBIR, we will optimize RNA formulations for GG delivery. With
further optimization, we hypothesize that GG delivery of RNA vaccines will offer substantial advantages over
current mRNA/LNP vaccines with respect to stability and safety while achieving comparable systemic
immunogenicity and superior mucosal immunogenicity. In Aim 1, we will identify an optimum formulation for GG
delivery of RNA vaccines including maximum loading, functional integrity, stability, and immunogenicity. In Aim
2, we will determine if GG delivery of influenza and SARS-CoV-2 RNA vaccines are stable at room temperature
or 4°C and can induce comparable or superior systemic or mucosal immune responses with lower reactogenicity
when compared LNP/RNA vaccines. If successful, these studies will provide an alternative RNA vaccine delivery
strategy with advantages in mucosal immunity, safety, stability, dose sparing, and pain/needle-free delivery.
Terms: <2019 novel corona virus><2019 novel coronavirus><2019-nCoV><2019-nCoV vaccine><Adverse Experience><Adverse event><Adverse reactions><Antibodies><Antibody Response><Antigen-Presenting Cells><Antigens><Biolistics><COVID-19><COVID-19 vaccine><COVID-19 virus><COVID19 virus><CV-19><Cell Body><Cells><Clinic><Clinical><Clinical Trials><CoV-2><CoV2><Coronavirus Infectious Disease 2019><Cryofixation><Cryopreservation><DNA><DNA Vaccines><DNA delivery><Deoxyribonucleic Acid><Developing Countries><Developing Nations><Devices><Dose><Dryness><Electroporation><Engineering><Environment><Epidermis><Formulation><Friends><Gene-Gun Technique><Glutathione><Gold><Grippe><Human><Immune><Immune response><Immunes><Immunity><Immunocompetent><Immunological response><In Vitro><Influenza><Influenza HA><Influenza Hemagglutinin><Intramuscular><Lead><Less-Developed Countries><Less-Developed Nations><Licensing><Life><Macaca><Macaque><Messenger RNA><Methods><Mice><Mice Mammals><Microinjections><Modeling><Modern Man><Mucosa><Mucosal Immune Responses><Mucosal Immunity><Mucosal Tissue><Mucous Membrane><Murine><Mus><Muscle><Muscle Tissue><Myocarditis><Naked DNA Vaccines><Names><Needles><Non-Polyadenylated RNA><Nucleic Acids><Pain><Pain Free><Painful><Painless><Pb element><Phase><Plasmids><Protamines><Protocol><Protocols documentation><RNA><RNA Degradation><RNA Gene Products><RNA Stability><RNA delivery><RNA vaccine><RNA-based vaccine><Recombinant DNA Vaccines><Replication Unit><Replicon><Ribonucleic Acid><Risk><Route><SARS corona virus 2><SARS-CO-V2><SARS-COVID-2><SARS-CoV-2><SARS-CoV-2 vaccine><SARS-CoV2><SARS-associated corona virus 2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-coronavirus-2 vaccine><SARS-related corona virus 2><SARS-related coronavirus 2><SARSCoV2><SBIR><Safety><Severe Acute Respiratory Coronavirus 2><Severe Acute Respiratory Distress Syndrome CoV 2><Severe Acute Respiratory Distress Syndrome Corona Virus 2><Severe Acute Respiratory Distress Syndrome Coronavirus 2><Severe Acute Respiratory Syndrome CoV 2><Severe Acute Respiratory Syndrome CoV 2 vaccine><Severe Acute Respiratory Syndrome-associated coronavirus 2><Severe Acute Respiratory Syndrome-related coronavirus 2><Severe acute respiratory syndrome associated corona virus 2><Severe acute respiratory syndrome coronavirus 2><Severe acute respiratory syndrome coronavirus 2 vaccine><Severe acute respiratory syndrome related corona virus 2><Skin><Small Business Innovation Research><Small Business Innovation Research Grant><T cell response><Technology><Temperature><Third-World Countries><Third-World Nations><Time><Transfection><Under-Developed Countries><Under-Developed Nations><Vaccine Antigen><Vaccines><Wuhan coronavirus><accessory cell><cardiac inflammation><cold preservation><cold storage><communicable disease transmission><coronavirus disease 2019><coronavirus disease 2019 vaccine><coronavirus disease 2019 virus><coronavirus disease-19><coronavirus disease-19 vaccine><coronavirus disease-19 virus><coronavirus infectious disease-19><deliver DNA><deliver vaccines><develop a vaccine><develop vaccines><developing country><developing nation><development of a vaccine><disease transmission><electroporative delivery><epidermis cell><flu HA><flu hemagglutinin><gamma-L-Glu-L-Cys-Gly><gamma-L-Glutamyl-L-Cysteinylglycine><gene electrotransfer><gene gun><hCoV19><heavy metal Pb><heavy metal lead><hesitant to vaccination><host response><immune competent><immune response to vaccination><immune response to vaccines><immune system response><immunogen><immunogenic><immunogenicity><immunoresponse><improved><infectious disease transmission><influenza viral HA><influenza viral hemagglutinin><influenza virus HA><influenza virus hemagglutinin><lipid based nanoparticle><lipid nanoparticle><mRNA><mRNA Degradation><mRNA Transcript Degradation><mRNA lipid nano particle vaccine><mRNA vaccine><mRNA-LNP based vaccine><mRNA-LNP combination vaccines><mRNA-LNP vaccines><mRNA-based vaccine><muscular><nCoV vaccine><nCoV-19 vaccine><nCoV19 vaccine><nCoV2><name><named><naming><nano particle delivery><nanoparticle delivered><nanoparticle delivery><next generation><non-painful><nonpainful><not painful><nuclease><pandemic><pandemic disease><particle><prevent><preventing><prototype><response><success><systemic inflammation><systemic inflammatory response><vaccination hesitancy><vaccine against 2019-nCov><vaccine against COVID-19><vaccine against SARS-CoV-2><vaccine against SARS-coronavirus-2><vaccine against Severe Acute Respiratory Syndrome CoV 2><vaccine against Severe acute respiratory syndrome coronavirus 2><vaccine associated immune response><vaccine candidates against SARS-CoV-2><vaccine delivery><vaccine development><vaccine for novel coronavirus><vaccine hesitancy><vaccine hesitant><vaccine immune response><vaccine immunogenicity><vaccine induced immune response><vaccines preventing COVID><vaccines to prevent COVID>