Universal Influenza A/B Vaccine

通用甲型/乙型流感疫苗

• 批准号: 10617390
• 负责人: Kenneth C Bagley
• 金额: $ 99.89万
• 依托单位: ORLANCE, INC.
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-07 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10617390
• 关键词: Antibodies; Antibody Response; Antigen-Presenting Cells; Antigens; Body Weight decreased; Cells; Clinical; Clinical Trials; Companions; DNA; DNA Vaccines; DNA delivery; Data; Development; Devices; Dose; Electroporation; Engineering; Exhibits; Ferrets; Formulation; Gold; Human; Humoral Immunities; Immune; Immune response; Immunologics; Inflammation; Inflammatory Response; Influenza; Influenza A virus; Influenza B Virus; Injections; Liquid substance; Lung; Macaca; Macaca fascicularis; Macaca mulatta; Modeling; Mucosal Immune Responses; Mucous Membrane; Mus; Pathogenesis; Phase; Population; Pre-Clinical Model; Preclinical Testing; Predisposition; Publishing; Reagent; Reporting; Role; Safety; Site; Skin; Small Business Innovation Research Grant; Strategic Planning; Syringes; T cell response; T-Lymphocyte; Testing; Toxic effect; United States National Institutes of Health; Vaccinated; Vaccination; Vaccine Antigen; Vaccines; Viral; Viremia; Virus; Virus Replication; design; experience; gene gun; immunogenicity; influenza virus strain; influenzavirus; innovation; next generation; nonhuman primate; novel; particle; pre-clinical; protective efficacy; response; safety assessment; universal influenza vaccine; unvaccinated; vaccine delivery; vaccine development; vaccine evaluation

Abstract Universal influenza vaccines should be possible if conserved antigens of influenza are effectively targeted and effective antiviral immune responses are generated against those antigens. DNA vaccination is an appealing approach for delivering universal influenza vaccines, however, natural immune responses to conserved influenza antigens are typically weak and most DNA vaccines tested in humans have not elicited robust humoral immunity. To overcome the obstacles to developing universal influenza DNA vaccines, we are using novel composite immunogens and delivering them with a next generation Gene Gun device that combines several engineering and formulation innovations that increase immunogenicity by increasing the number of skin cells and antigen presenting cells expressing vaccine antigen. We have already obtained encouraging results with a universal influenza A (UFluA) DNA vaccine. Under this SBIR proposal, we intend to test a companion universal influenza B (UFluB) DNA vaccine to create a more comprehensive universal A/B vaccine (UFluA/B) that will provide broad protective coverage from all influenza A and B types capable of infecting humans. If we are successful at demonstrating that a single UFluA/B DNA vaccine can induce broad responses and protection in mice in the phase I effort, we will advance this this product to preclinical testing under the phase II portion of this application where we will investigate immunogenicity and protective efficacy in naïve and pre-immune ferrets and safety and efficacy in a nonhuman primate model that closely resembles humans in their dosing, immune response to DNA vaccination and susceptibility to influenza. If successful, these data will provide Orlance with a strong preclinical IND data package to advance this strategy to phase I human clinical trials. 2

摘要 如果流感的保守抗原被有效地靶向， 针对这些抗原产生有效的抗病毒免疫反应。DNA疫苗是一种吸引人的 然而，提供通用流感疫苗的方法， 抗原通常是弱的，并且在人体中测试的大多数DNA疫苗没有引起强的体液免疫。 为了克服开发通用流感DNA疫苗的障碍，我们正在使用新的复合材料， 免疫原，并通过下一代基因枪装置将其递送，该装置结合了几种工程技术， 以及通过增加皮肤细胞和抗原的数量来增加免疫原性的配方创新 呈递细胞表达疫苗抗原。我们已经取得了令人鼓舞的成果， 甲型流感（UFluA）DNA疫苗根据这项SBIR提案，我们打算测试一种伴随的通用流感 B（UFluB）DNA疫苗，以创建更全面的通用A/B疫苗（UFluA/B）， 保护性覆盖能够感染人类的所有甲型和B型流感。如果我们成功地 证明了单一UFluA/B DNA疫苗可以在小鼠中诱导广泛的应答和保护， 第一阶段的努力，我们将推进这一产品的临床前测试，在第二阶段的部分，这一申请 在那里，我们将研究免疫原性和保护效力在幼稚和免疫前雪貂和安全性， 在非人灵长类动物模型中的有效性，该模型在给药、对DNA的免疫应答 接种疫苗和流感易感性。如果成功，这些数据将为Orlance提供强大的临床前研究。 IND数据包将该策略推进至I期人体临床试验。2