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: 8642227
• 负责人: Jenny P Ting
• 金额: $ 360.31万
• 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/8642227
• 关键词: Academia; Adjuvant; Animal Model; Applications Grants; Biotechnology; Chemistry; Dengue Virus; Dose; Drug Formulations; FDA approved; Goals; Human; Immune response; Immune system; Immunity; Immunology; Industry; Medical; Molds; Molecular; Mus; Nanotechnology; North Carolina; Pattern; Porosity; Process; Property; Public Health; Science; Shapes; System; Technology; Testing; Translations; Universities; Vaccine Adjuvant; Vaccines; Viral; Virus; Virus Diseases; base; flexibility; influenzavirus; lithography; microbial; nanoparticle; novel; particle; pathogen; vaccine delivery; virology

DESCRIPTION (provided by applicant): 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 Nonwetting 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 PRINTNP 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. RELEVANCE: The overarching purpose of this project is to deliver vaccines and adjuvants that can activate the innate and adaptive immune systems through a nano-technology platform that is precise in formulation and uniformed in properties. We will focus on vaccines for high medical need viral infections, which are of broad importance in public health. The end goal is to achieve an optimal nanoparticle-based vaccine platform.

描述(由申请人提供)：这项U19中心拨款申请的主要目的是优化一种用于输送疫苗和疫苗佐剂的新型纳米颗粒(NP)平台。这项应用是跨学科的，需要材料科学、免疫学、病毒学和动物模型方面的专业知识。我们将对这一平台进行两种高度医疗需求的病毒测试：流感和登革病毒。一旦优化，这一平台应该能够适应各种微生物病原体疫苗的交付。NP技术平台的独特之处在于应用了一种名为在非润湿模板(印刷)中复制颗粒的软性光刻颗粒成型工艺来生产颗粒。这项技术是由北卡罗来纳大学的约瑟夫·德西蒙博士开发的，他也是生物技术公司Liqudia Technologies的创始人。印刷品的一个主要优点是产生的NPs是免疫惰性的，具有精确的大小、化学成分、孔隙率、弹性和形状。重要的是，我们的工业合作伙伴Liqudia可以大量生产GMP(良好制造规范)质量的印刷NPs。一种标准的Print-NP已经用于提供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。该应用程序有三个以北卡罗来纳大学为基地的项目，由包括产业界和学术界伙伴关系在内的四个核心提供支持。所有这三个项目都高度相互关联，最终目标是使IND最终应用于优化的疫苗/佐剂生物制品。第一个项目将优化PRINTNP的化学成分，以提高作为疫苗递送系统的生物效力。第二个项目将集中在联合传递PAMPs(病原体相关分子模式)作为佐剂，以刺激小鼠和适当的大型动物模型的抗病毒免疫。第三个项目将使用一种新的人源化小鼠系统来评估人类对NP递送的疫苗和佐剂的免疫反应。这三个项目高度整合，以发现疫苗和佐剂在人类体内翻译所需的最优Print-NP平台。 相关性：该项目的主要目的是提供疫苗和佐剂，通过一个配方精确、特性统一的纳米技术平台，激活先天和适应性免疫系统。我们将把重点放在针对高度医疗需求的病毒感染的疫苗上，这对公共卫生具有广泛的重要性。最终目标是实现一个最佳的基于纳米颗粒的疫苗平台。