The defining characteristics of Type 1 diabetes is the production of B- and T-cell immunity towards beta-cells in the pancreas. Vaccine approaches to restore antigen-specific immune tolerance to pancreatic beta-cell antigens without global immune suppression are potential therapeutic interventions for Type 1 diabetes. However, a method for realizing both efficacy and safety is yet to be developed. A major challenge in the development of effective vaccines is efficient delivery of vaccine components to antigen presenting cells (APCs) in lymphoid organs, where the orchestrations of immune cells are initiated.<br/>Here we show a molecular approach which targets immune suppressive vaccine to lymph nodes results in enhanced protection from disease in animal models. Helper T cells (T<sub>H</sub> cells) Peptides are conjugated to an amphiphilic polymer and upon s.c. injection, accumulate in the antigen presenting cells in the draining lymph nodes. Peptide amphiphililes triggers peptide/MHC II signal without co-stimulatory molecules, resulting in differentiation of cells that have characteristics of regulatory T cells. Treatment of NOD mice with lymph node-targeting peptide vaccines significantly delayed and reduced the incidence of diabetes. This is associated with significant suppression of antoreactive CD4 T cells and increased frequency of regulatory T cells, as well as increased suppressive cytokine productions. Our findings suggest antigen delivery to lymph nodes via albumin-hitchhiking might be broadly applicable to treat autoimmune diseases. <br/>

Engineering lymph-node targeting vaccines for type 1 diabetes

253rd National Meeting (2017)

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