Novel Nanoparticle Platform for the delivery of Vaccines and Adjuvants

这项U19中心资助申请的主要目的是优化一种新型纳米颗粒(NP) 提供疫苗和疫苗佐剂的平台。应用程序是跨学科的，需要 材料科学、免疫学、病毒学和动物模型方面的专业知识。我们将为两个人测试这个平台 高度医疗需要的病毒：流感和登革热病毒。优化后，该平台应该是 适用于提供针对各种微生物病原体的疫苗。NP技术平台 其独特之处在于应用了一种称为颗粒复制的软性光刻颗粒成型工艺 非润湿模板(打印)以产生颗粒。这项技术是由约瑟夫博士开发的 北卡罗来纳大学的DeSimone，他也是生物技术公司Liqudia的创始人 技术。印刷品的一个主要优点是产生的NPs在免疫上是惰性的，并且是 精确的尺寸、化学成分、孔隙度、弹性和形状。重要的是，GMP(良好制造规范) 我们的工业合作伙伴Liqudia可以大量生产高质量的印刷品-NPs。一种标准 Print-NP已被用于提供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，并进一步提供了节省剂量的效果。 这个应用程序有三个基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 合伙企业。所有这三个项目都高度相关，并且最终目标是实现 IND在优化疫苗/佐剂生物制品方面的应用。第一个项目将优化Print-NP 作为疫苗递送系统的增强生物效力的化学。第二个项目将重点放在 共传递PAMPs(病原体相关分子模式)作为佐剂刺激抗病毒免疫 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的人性化鼠标系统来 评估人类对NP提供的疫苗和佐剂的免疫反应。这三个项目都是高度 整合以发现疫苗和佐剂递送所需的最佳Print-NP平台 在人类身上进行翻译。

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.