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.

该U19中心赠款应用的总体目的是优化新型纳米颗粒（NP） 提供疫苗和疫苗佐剂的平台。该申请是跨学科的，需要 物质科学，免疫学，病毒学和动物模型的专业知识。我们将对两个 高医疗需求的病毒：流感和登革热病毒。一旦优化，该平台应该是 适应疫苗针对多种微生物病原体的疫苗。 NP技术平台 通过在称为粒子复制的软光刻粒子成型过程中应用的区别 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，他还创立了Liquidia生物技术公司 技术。打印的主要优点是，生产的NP是免疫学上的，是 精确的大小，化学，孔隙率，柔韧性和形状。重要的是，GMP（良好的制造实践） 我们的工业合作伙伴Lilesia可以大量制造优质的NP。标准 Print-NP已用于传递FDA批准的疫苗，并进行初步结果表明这一点 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的效果。 该应用程序在UNC上有三个项目，并得到包括行业 - academia在内的四个核心的支持 伙伴关系。这三个项目都是高度相关的，并且具有实现最终的最终目标 用于优化疫苗/辅助生物制剂的IND应用。第一个项目将优化print-np 化学以增强生物学功效为疫苗输送系统。第二个项目将重点放在 辅助剂的辅助症（病原体相关分子模式）的共同传递，以刺激抗病毒免疫力 在小鼠和适当的大动物模型中。第三个项目将使用新颖的人源化鼠标系统来 评估人类对NP释放的疫苗和辅助的免疫反应。这三个项目很高 集成以发现疫苗和辅助输送所需的最佳印刷NP平台 人类翻译。