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

临床就绪的 MACH-1 基因枪，用于提供通用流感 DNA 疫苗

• 批准号: 10761364
• 负责人: Hannah Frizzell
• 金额: $ 99.65万
• 依托单位: ORLANCE, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10761364
• 关键词: Acceleration; Address; Animals; Antibodies; Antibody Avidity; Antigen Presentation; Antigens; Area; CD8-Positive T-Lymphocytes; Cells; Clinic; Clinical; Communicable Diseases; Conserved Sequence; Cryopreservation; DNA; DNA Vaccines; DNA delivery; Data; Development; Devices; Disease; Documentation; Dose; Dryness; Electroporation; Engineering; Epitopes; Exclusion; Feedback; Formulation; Friends; Funding; Future; Gases; Generations; Gold; Helium; Housing; Human; Hydrogen; Immune Evasion; Immune response; Immunity; Influenza; Investigational Drugs; Lead; Life; Malignant Neoplasms; Manuals; Methods; Modification; Molecular Conformation; Mucosal Immune Responses; Mucosal Immunity; Needles; Pain Free; Painless; Particle Size; Penetration; Performance; Phase; Phase I Clinical Trials; Powder dose form; Power Sources; Process; RNA; RNA vaccine; Reproducibility; Rodent; Rotation; Safety; Skin; Small Business Innovation Research Grant; Speed; Standardization; Stream; System; T cell response; Technology; Temperature; Testing; Time; Vaccine Design; Vaccines; Variant; Viral; Virus; clinic ready; clinical trial readiness; design; future pandemic; gene gun; human subject; immunogenicity; improved; influenza virus strain; innovation; lipid nanoparticle; manufacturing process; mouse model; mucosal site; nonhuman primate; pandemic influenza; particle; phase I trial; porcine model; portability; pre-Investigational New Drug meeting; pre-clinical; pressure; prevent; protective efficacy; scale up; transmission process; universal influenza vaccine; vaccine delivery; vaccine formulation; vaccine immunogenicity

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.

项目概要 Orlance 开发了一种领先的通用流感 (UFlu) DNA 疫苗，以满足对以下疫苗的需求： 可以预防年度流感和可能导致未来大流行的新变种的出现。我们的 UFlu 疫苗是一种多剂量疫苗，旨在诱导全身和粘膜免疫反应， 通过诱导广泛的传播来预防传播并最大限度地减少当前流行和新出现的菌株造成的疾病 针对所有流感中常见的保守病毒序列的抗体和细胞免疫反应 亚型。在之前的 SBIR 资助下，我们证明了我们的基因枪 (GG) 提供的 UFlu DNA 疫苗 诱导广泛特异性（通用）抗体和 T 细胞反应以及针对多种流感的保护 啮齿动物和非人类灵长类动物面临的挑战。该疫苗即将进入第一阶段人体试验，需要 诊所准备好 GG 设备来管理它。在这里，我们建议继续开发我们有前途的 MACH-1TM GG 向人类提供先导 UFlu DNA 疫苗和其他先导疫苗。 MACH-1 是一种无针装置 使用高压气体将 DNA 和/或 RNA 包被的金微粒直接输送到表皮细胞中。 它无痛，与其他药物相比，需要低剂量的 DNA 或 RNA 来诱导保护性免疫 交付方法，并经过多项创新设计，以最大限度地提高效率和可重复性 交货。在这里，我们将： 通过使其便携且更易于使用来改进 MACH-1（目标 1）；制定 GMP- 可扩展的 DNA 疫苗配方填充并完成一次性剂量单位（目标 2），并评估安全性， 改进的 MACH-1 UFlu 疫苗在小鼠和猪模型中的免疫原性和功效 （目标 3）。成功完成这些目标将使新药研究 (IND) 成为可能 推进我们的 MACH-1 所需的输送系统设备和配方平台的文档 将 UFlu DNA 疫苗交付至第一阶段试验。