Type 1 diabetes (T1D) is an autoimmune disease where islets are attacked by the immune system. Existing therapies broadly suppress immune function, but a new idea aims to reprogram the immune response using vaccine-like treatments. This idea involves co-delivering islet auto-antigens and regulatory cues. The goal is to polarize antigen-specific T cells toward regulatory T cells (TREG) - a regulatory phenotype that blocks autoimmune reactions. Lymph nodes (LN) are sites where adaptive immune responses develop, and are tissues these treatments must reach for efficacy. We developed a strategy to directly deposit immune signals in LNs using biodegradable carriers co-encapsulating self-antigens and regulatory signals. Depots are directly injected to LNs, but are are too large to drain from nodes. Instead, they slowly degrade, providing local controlled release to condition the LN environment for tolerance. Depots co-encapsulating CgA, an islet –autoantigen, and rapamycin – a regulatory cue, were injected to mouse LNs followed by infusion of CgA-specific T cells (Fig. 1A). Analysis revealed CgA/Rapa MPs reduced T cell proliferation (Fig. 1B) and increased TREG differentiation (Fig. 1C), indicating depots promoted a tolerogenic T cell response. To investigate the ability of CgA/Rapa MPs to inhibit T1D, NOD mice were immunized i.LN with CgA/Rapa MPs, and disease incidence was monitored. Strikingly, a single injection of CgA/Rapa MPs delayed spontaneous T1D onset for over 20 weeks compared to untreated mice (Fig. 1D), supporting i.LN depots as a platform to promote tolerance in T1D.

Intra-lymph node vaccine depots to promote selective tolerance in type 1 diabetes

2019 Spring National Meeting

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