Engineering Monodisperse Particulate Vaccines to Tailor Immunological Responses

设计单分散颗粒疫苗以定制免疫反应

• 批准号: 9337971
• 负责人: Jenny P Ting
• 金额: $ 13.23万
• 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 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9337971
• 关键词: Address; Adjuvant; Adult; Affect; Animals; Antibody Response; Antigens; Attenuated; Attenuated Live Virus Vaccine; Biocompatible; Categories; Chemicals; Clinical Trials; Cyclic GMP; Dengue; Dengue Infection; Dengue Virus; Development; Dose; Elderly; Emerging Communicable Diseases; Engineering; Equilibrium; Face; Ferrets; Film; Flavivirus; Formulation; Generations; Guidelines; Human; Immune response; Immunoglobulin G; Industry; Infection prevention; Influenza; Influenza Therapeutic; Learning; Licensing; Life; Medical; Microbe; Molds; Mus; National Institute of Allergy and Infectious Disease; Nature; Online Systems; Particle Size; Particulate; Peptides; Pharmaceutical Preparations; Play; Process; Production; Public Health; Safety; Serotyping; Shapes; Subunit Vaccines; Technology; Time; Translating; Vaccination; Vaccine Adjuvant; Vaccine Design; Vaccines; Viral; Virus; adaptive immunity; base; combat; density; design; economic impact; flexibility; humanized mouse; immunogenic; influenza virus vaccine; influenzavirus; manufacturing process; microorganism; mouse model; nanoparticle; neutralizing antibody; nonhuman primate; novel; particle; pathogen; product development; programs; response; scale up; seasonal influenza; trafficking; vaccine delivery; vaccine development

This project is focused on the development of a unique GMP-compliant particle molding technology that we have pioneered called PRINT� (Particle Replication in non-wetting templates) as a delivery platform for particulate multivalent vaccines targeting influenza and Dengue viruses. PRINT provides complete control over particle size, shape and chemical composition, and enables the systematic tailoring of antigen proximity to the particle, antigen density and particle size and shape to screen and identify the optimal particle parameters to elicit enhanced immunological responses. The down-selected particle parameters will provide design rules to manufacture influenza and dengue particulate multivalent vaccines to investigate the ability to generate a complete and robust neutralizing antibody response to each antigen. Also, additional Projects within our Program will utilize these multivalent particulate vaccines to address the use of novel adjuvants to modulate the immune response. These particulate vaccines will be evaluated in a humanized mouse model to determine how to prevent infection of homotypic or all 4 dengue virus serotypes. We will combine the learning from each Project to scale-up the most promising multivalent particulate vaccines and advance these to large animal challenge studies for both influenza and dengue. Due to the immediate medical need for multivalent vaccines for influenza and dengue and the cGMP-compliant nature of our particle molding technology, the formulations can be advanced into product development for human trials.

该项目的重点是开发一种独特的符合 GMP 要求的颗粒成型技术，我们首创了这种技术，称为 PRINT�（非润湿模板中的颗粒复制），作为针对流感和登革热病毒的颗粒多价疫苗的递送平台。 PRINT 可以完全控制颗粒尺寸、形状和化学成分，并能够系统地调整抗原与颗粒的接近度、抗原密度以及颗粒尺寸和形状，以筛选和识别最佳颗粒参数，从而引发增强的免疫反应。向下选择的颗粒参数将为制造流感和登革热颗粒多价疫苗提供设计规则，以研究对每种抗原产生完整且强大的中和抗体反应的能力。此外，我们计划中的其他项目将利用这些多价颗粒疫苗来解决使用新型佐剂来调节免疫反应的问题。这些颗粒疫苗将在人源化小鼠模型中进行评估，以确定如何预防同型或所有 4 种登革热病毒血清型的感染。我们将结合每个项目的经验来扩大最有前途的多价颗粒疫苗的规模，并将其推进针对流感和登革热的大型动物挑战研究。由于对流感和登革热多价疫苗的迫切医疗需求以及我们的颗粒成型技术符合 cGMP 的性质，这些配方可以进入人体试验的产品开发阶段。