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

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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.