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

项目摘要 Orlance开发了一种领先的通用流感（UFlu）DNA疫苗，以满足对疫苗的需求， 可以防止每年的流感和可能导致未来大流行的新变种的出现。我们 UFlu疫苗是一种多剂量疫苗，旨在诱导全身和粘膜免疫应答， 通过诱导广泛传播，防止传播并最大限度地减少目前流行和新出现的菌株的疾病 抗体和细胞免疫反应，靶向所有流感病毒共有的保守病毒序列 亚型在之前的SBIR资助下，我们证明了我们的基因枪（GG）递送的UFlu DNA疫苗 诱导广泛特异性（通用）抗体和T细胞反应并预防多种流感 啮齿类动物和非人类灵长类动物的挑战。该疫苗已接近第一阶段人体试验， 在这里，我们建议继续开发我们有前途的MACH-1 TM GG 向人类提供UFlu DNA疫苗和其他疫苗。MACH-1是一种无针器械 其使用高压气体将DNA和/或RNA包被的金微粒直接递送到表皮细胞中。 它是无痛的，与其他疫苗相比，它需要低剂量的DNA或RNA来诱导保护性免疫。 交付方法，并已设计了几项创新，以最大限度地提高效率和再现性 的交付。在这里，我们将：改进MACH-1，使其便携和更容易使用（目标1）;开发GMP- 将可扩展的DNA疫苗制剂装入填充和完成的一次性给药单元（Aim 2），并评估安全性， 在小鼠和猪模型中通过改良MACH-1递送的UFlu疫苗的免疫原性和有效性 (Aim 3）。这些目标的成功完成将导致研究性新药（IND）-启用 推进我们的MACH-1所需的输送系统设备和制剂平台的文档 将UFlu DNA疫苗交付给第一阶段试验。

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.