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.

项目摘要 Orlance已开发出一种铅普遍流感（UFLU）DNA疫苗，以满足对疫苗的需求 可以防止年度流感和可能导致未来大流行的新变体的出现。我们的 UFLU疫苗是一种多剂量疫苗，旨在诱导系统性和粘膜免疫反应 通过诱导广泛 抗体和细胞免疫反应靶向所有流感中常见的保守病毒序列 亚型。在先前的SBIR资金下，我们证明了我们的基因枪（GG）释放的UFLU DNA疫苗 诱导广泛特异性（通用）抗体和T细胞反应以及免受各种流感的保护 啮齿动物和非人类灵长类动物的挑战。该疫苗正在接近1期的人类试验，将需要 诊所就绪GG设备进行管理。在这里，我们建议继续开发有前途的Mach-1TM GG 向人类输送铅UFLU DNA疫苗和其他铅疫苗。 Mach-1是无针的设备 这样，使用高压气体将DNA-和/或RNA涂层的金微粒直接传递到表皮细胞中。 它不疼痛，与其他 交付方法，并通过几项创新进行了设计，以最大程度地提高效率和可重复性 交货。在这里，我们将：通过使其便携式且易于使用来改善MACH-1（AIM 1）；发展GMP- 可伸缩的DNA疫苗配方成填充和完成一次性剂量单元（AIM 2），并评估安全性， 改善MACH-1在小鼠和猪模型中提供的MACH-1传递的UFLU疫苗的免疫原性和功效 （目标3）。这些目标的成功完成将导致调查新药（IND）增强 交付系统设备和配方平台的文档，以推动我们的Mach-1 将UFLU DNA疫苗传递到1期试验。