High-Throughput Evaluation of Dendritic Cell-Targeting Vaccine Particles for the

描述（由申请人提供）：这项工作代表了一项基于生物材料的生物医学工程研究计划，结合了针对耐受性的免疫学。具体而言，该项目侧重于技术工程，以提供个性化的高通量筛选免疫细胞对基于微粒的疫苗的反应，使用有限数量的细胞。基于微粒的疫苗系统可以在体内将抗原和相关免疫调节因子传递给目标吞噬细胞群，特别是树突状细胞，这是一种关键的免疫调节剂。对诱导耐受性的疫苗的典型评估依赖于一次测试一种制剂，希望发现能够产生长期免疫耐受性的单一因素。然而，多种关键信号可能结合起来促进稳健、持久的抗原特异性耐受性。缺乏对不同免疫调节因子之间相互作用的了解，以及缺乏检测大量因子组合的有效手段，是开发新疫苗技术的一个重大障碍。为了克服这一障碍，我们正在开发一种基于细胞的高通量微阵列方法，用于检测含有多种成分的靶向树突状细胞（一种关键的抗原呈递细胞类型）的微粒。我们的初步数据表明，我们正在开发的独特的高通量体外平台是可行的，并且微颗粒配方的体外筛选可以用于提示注射微颗粒的体内反应。我们的长期试验台应用是通过注射微粒预防糖尿病小鼠模型中的1型糖尿病。我们正在优化多组分颗粒配方，以指导dc向耐受性表型和诱导调节性t细胞进行抗原特异性免疫抑制。我们的微型化技术只需要少量的细胞，朝着个性化疫苗的发展迈出了一步。

DESCRIPTION (provided by applicant): This work represents a biomaterials-based biomedical engineering research program integrated with immunology directed toward tolerance. Specifically, this project focuses on the engineering of technologies to provide personalized high-throughput screening of immune cell response to microparticle-based vaccines, using a limited number of cells. Microparticle-based vaccine systems can, in vivo, deliver antigen and relevant immuno- modulatory factors to targeted phagocytic cell population, specifically, dendritic cells, a key immune regulator. Typical assessment of a tolerance-inducing vaccine relies on testing one formulation at a time, hoping to uncover a single factor capable of generating long-lived immune tolerance. However, multiple critical signals are likely to combine to promote robust, enduring antigen-specific tolerance. A lack of understanding of the interactions between different immunomodulatory factors, and the lack of an efficient means to test large numbers of combinations of factors represents a significant blockade for the development of new vaccine technologies. In order to overcome this barrier, we are developing a high-throughput cell-based microarray approach for the testing of microparticles incorporating multiple components targeted to dendritic cells, a key antigen presenting cell type. Our preliminary data indicates that the unique high- throughput in vitro platform we are developing is feasible, and that in vitro screening of microparticle formulations can be useful for suggesting in vivo responses to injected microparticles. Our long-term test-bed application is the prevention of type-1 diabetes in a diabetic mouse model by injection of microparticles. We are optimizing multi- component particle formulations to direct DCs toward a tolerogenic phenotype and the induction of regulatory T-cells for antigen-specific immune suppression. Our miniaturized technology requires only small numbers of cells, taking steps toward the development of personalized vaccines.