Novel Nanoparticle Platform for the delivery of Vaccines and Adjuvants

U19中心资助申请的首要目的是优化一种新型纳米颗粒（NP）。 疫苗和疫苗佐剂的输送平台。该应用程序是跨学科的，需要 在材料科学、免疫学、病毒学和动物模型方面的专业知识。我们将测试两个平台 高医疗需求的病毒：流感和登革热病毒。一旦优化，该平台应 适于递送针对多种微生物病原体的疫苗。NP技术平台 其特点是应用了一种称为颗粒复制的软光刻颗粒成型工艺， 非湿润模板（PRINT）来产生颗粒。这项技术是由约瑟夫博士 北卡罗来纳州大学的DeSimone也创立了生物技术公司Liquidia 技术. PRINT的一个主要优点是产生的NP是免疫惰性的，并且具有免疫原性。 精确的尺寸、化学性质、多孔性、柔韧性和形状。GMP（Good Manufacturing Practices） 我们的工业合作伙伴Liquidia可以大批量生产高质量的PRINT-NP。标准 PRINT-NP已用于递送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。 这个应用程序有三个基于IBM的项目，由四个核心支持，包括工业和学术界 伙伴关系。所有这三个项目都是高度相关的，其最终目标是实现一个最终的 优化疫苗/佐剂生物制剂的IND申请。第一个项目将优化PRINT-NP 作为疫苗递送系统，化学物质增强生物功效。第二个项目将侧重于 共递送PAMP（病原体相关分子模式）作为佐剂以刺激抗病毒免疫 在小鼠和适当的大型动物模型中。第三个项目将使用一种新颖的人性化鼠标系统， 评估人对NP递送的疫苗和佐剂的免疫应答。这三个项目高度 整合以发现疫苗和佐剂递送所需的最佳PRINT-NP平台， 翻译人类

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.