Novel Nanoparticle Platform for the delivery of Vaccines and Adjuvants

用于输送疫苗和佐剂的新型纳米颗粒平台

• 批准号: 9307701
• 负责人: Jenny P Ting
• 金额: $ 466.6万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9307701
• 关键词: Academia; Adaptive Immune System; Adjuvant; Animal Model; Applications Grants; Biotechnology; Chemistry; Dengue Virus; Dose; FDA approved; Formulation; Goals; Human; Immune response; Immunity; Immunologics; Immunology; Industrialization; Industry; Instruction; Medical; Molds; Molecular; Mus; Nanotechnology; North Carolina; Pattern; Porosity; Process; Property; Public Health; Shapes; System; Technology; Testing; Translations; Universities; Vaccines; Virus; Virus Diseases; antiviral immunity; base; flexibility; humanized mouse; influenzavirus; lithography; materials science; microbial; nanoparticle; novel; particle; pathogen; vaccine delivery; virology

The overarching purpose of this U19 Center grant application is to optimize a novel nanoparticle (NP) platform for the delivery of vaccines and vaccine adjuvants. The application is cross-disciplinary and requires expertise in material sciences, immunology, virology and animal models. We will test this platform for two viruses of high-medical need: influenza and Dengue virus. Once optimized, this platform should be adaptable for the delivery of vaccines against a variety of microbial pathogens. The NP technology platform is distinguished by the application of a soft lithography particle molding process called Particle Replication In Non-wetting Templates (PRINT) to produce the particles. This technology was developed by Dr. Joseph DeSimone at the University of North Carolina, who also founded the biotechnology company, Liquidia Technologies. A major advantage of PRINT is that the NPs produced are immunologically-inert and are of precise size, chemistry, porosity, flexibility and shape. Importantly, GMP (Good Manufacturing Practices) quality PRINT-NPs can be fabricated in large quantities by our industrial partner, Liquidia. A standard PRINT-NP has been used to deliver FDA-approved vaccines, with preliminary results demonstrating that this delivery system enhanced immunity compared to soluble vaccine and further provided a dose-sparing effect. This application has three projects based at UNC, supported by four cores that include industry-academia partnerships. All three projects are highly inter-related and have the ultimate goal of enabling an eventual IND application for optimized vaccine/adjuvant biologics. The first project will optimize the PRINT-NP chemistries to enhance biologic efficacy as a vaccine delivery system. The second project will focus on the co-delivery of PAMPs (Pathogen-associated Molecular Patterns) as adjuvants to stimulate anti-viral immunity in mice and appropriate larger animal models. The third project will use a novel humanized mouse system to assess human immune responses to NP-delivered vaccine and adjuvant. The three projects are highly integrated to discover the most optimal PRINT-NP platform needed for vaccine and adjuvant delivery for translation in humans.

U19 中心拨款申请的首要目的是优化新型纳米颗粒 (NP) 疫苗和疫苗佐剂的输送平台。该申请是跨学科的，需要 材料科学、免疫学、病毒学和动物模型方面的专业知识。我们将测试这个平台的两个 高医疗需求病毒：流感和登革热病毒。一旦优化，这个平台应该 适用于输送针对多种微生物病原体的疫苗。 NP技术平台 其特点是应用了称为“粒子复制”的软光刻粒子成型工艺 用于产生颗粒的非润湿模板（打印）。这项技术是由约瑟夫博士开发的 DeSimone 是北卡罗来纳大学的教授，也是生物技术公司 Liquidia 的创始人 技术。 PRINT 的一个主要优点是产生的 NP 具有免疫惰性并且具有 精确的尺寸、化学成分、孔隙率、灵活性和形状。重要的是，GMP（良好生产规范） 我们的工业合作伙伴 Liquidia 可以大批量生产高质量的 PRINT-NP。一个标准 PRINT-NP 已用于交付 FDA 批准的疫苗，初步结果表明， 与可溶性疫苗相比，递送系统增强了免疫力，并进一步提供了剂量节省效应。 该应用程序有三个位于北卡罗来纳大学的项目，由包括工业界和学术界在内的四个核心支持 伙伴关系。所有三个项目都高度相互关联，其最终目标是实现最终的 优化疫苗/佐剂生物制剂的 IND 申请。第一个项目将优化 PRINT-NP 化学物质可增强疫苗输送系统的生物功效。第二个项目将重点关注 共同递送 PAMP（病原体相关分子模式）作为佐剂以刺激抗病毒免疫 在小鼠和适当的较大动物模型中。第三个项目将使用一种新颖的人性化鼠标系统 评估人体对 NP 疫苗和佐剂的免疫反应。这三个项目都具有很高的 整合以发现疫苗和佐剂输送所需的最佳 PRINT-NP 平台 人类的翻译。