Autoimmune diabetes (type 1 diabetes; T1D) is a disease of failed immune regulation. A vaccine for T1D aims to use antigenic material to stimulate regulatory immune responses and restore immune homeostasis. Challenges for successful implementation include finding the best mode of delivery and the best adjuvant for the vaccine to be effective. We have assembled a team of experts in biomaterials and T1D to address these challenges. The goal of this work is to investigate the delivery of relevant vaccine components incorporated into a controlled release biomaterial delivery system for a T1D vaccine. The ability to target and deliver immunomodulating factors in a controlled way to critical immune cell types is key. Our strategy involves the injectable administration of factors (e.g., antigen and adjuvant) formulated in an injectable, in-situ forming hydrogel co-mixed with adjuvant and biodegradable microparticles encapsulating insulin antigen. The adjuvant strategy taken here is along the lines of recent clinical trials for T1D (showing safety but not efficacy), administering pro-inflammatory adjuvants plus antigen with the expectation that inflammation can be resolved with subsequent tolerance to pancreatic antigen. This biomaterial delivery system serves as a temporary microenvironment to attract and educate immune cells. We hypothesize this biomaterial-based vaccine system will recruit and educate immune cells to become tolerant of insulin, ameliorating T1D. The proposed research is innovative, representing targeted, controlled delivery of vaccine components aiming to restore tolerance to T1D self-antigens. Our in vivo preliminary data demonstrate that our approach is promising for the amelioration of T1D.
Type-1 diabetes is an autoimmune disease with enormous personal and economic impact in the US. Therapeutic vaccination approaches for type-1 diabetes hold promise to correct these autoimmune responses. The objective of this application is to engineer a biomaterials-based system with controlled release and targeting properties, as an injectable vaccine to retrain the immune system to toward diabetes relevant self-antigen.
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