Project Summary We propose to develop a new immunogenicity assay and machine learning based framework for creating tolerization vaccines for autoimmune diseases with improved population coverage. In collaboration with Harvard University and the University of Massachusetts Chan Medical School Diabetes Center of Excellence we will develop a new assay, the Multiplexed Multi-antigen Activation Assay (MMAA), to discover self- antigens that are recognized by cytotoxic T cells in Type 1 Diabetes (T1D) (Aim 1). We will use the self-antigens we have confirmed to design novel multi-epitope tolerization vaccines and test the vaccines for their ability to expand CD4+ TReg cells in PBMCs from T1D donors (Aim 2). We will utilize new machine learning methods to modify and select vaccine epitopes to substantially improve tolerization vaccine population coverage. Our products will be the resulting vaccines.

Project Narrative Autoimmune diseases are caused by immune system cells that have escaped normal controls and inappropriately seek out our normal cells for destruction. These bad killer cells recognize specific normal protein sequences on a cell’s surface as a signal to kill it. We will develop an assay to discover what sequences these bad killer cells recognize, and use the assay to discover normal sequences relevant to Type 1 Diabetes. Once we know what normal sequences these killer cells recognize we can use the sequences to design a vaccine that regulates their killing.