Engineering Monodisperse Particulate Vaccines to Tailor Immunological Responses

设计单分散颗粒疫苗以定制免疫反应

基本信息

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
项目类别：
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

项目摘要

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的粒子成型技术，我们已经开创了称为Print（非润湿模板中的粒子复制），作为靶向多价疫苗的递送平台。打印提供了对粒径，形状和化学成分的完整控制，并可以实现抗原接近粒子，抗原密度以及粒径和形状的系统剪裁，以筛选并识别最佳粒子参数以引起增强的免疫学反应。下降的粒子参数将提供设计规则，以制造影响和登革热特定的多价疫苗，以研究对每种抗原产生完整且可靠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特定疫苗来解决新型调节器调节免疫的使用。回复。这些特定的疫苗将在人源化的小鼠模型中评估，以确定如何防止同型感染或所有4种风扇病毒血清型。我们将从每个项目中结合学习，以扩大最有希望的多价特定疫苗，并将这些疫苗推向影响力和粉丝的大型动物挑战研究。由于对影响力和粉丝的多价疫苗以及我们粒子成型技术的符合CGMP兼容的性质的直接医疗需求，该公式可以推进到人类试验的产品开发中。