Synthetically glycosylated antigens as an inverse vaccine platform to prevent and treat food allergies

Abstract

The only FDA-approved oral immunotherapy for a food allergy provides protection against accidental exposure to peanuts. However, this therapy often causes discomfort or side effects and requires long-term commitment. Better preventive and therapeutic solutions are urgently needed. We have developed a technology for inverse vaccination using glyco-polymerized antigens to induce antigen-specific non-responsiveness. We have demonstrated that following subcutaneous (SC) administration, glyco-polymer conjugates traffic to draining lymph nodes (LNs) and are preferentially internalized by antigen presenting cells, educating the immune system to respond to these antigens in an innocuous way. Here, we tested SC administration of glyco-polymerized β-lactoglobulin (BLG) in a murine model of cow’s milk allergy. Two doses of glyco-polymerized BLG given one week apart (prior to sensitization) prevented an allergic response to BLG upon intragastric challenge as measured by reductions in BLG-specific IgG, IgG1, and IgE production as well as BLG-specific type 2 T helper cell (Th2) responses in vitro. We further explored the therapeutic potential of glyco-polymerized BLG. Unlike unmodified BLG, two SC injections of glyco-polymerized BLG after sensitization did not cause anaphylactic reactions in allergic mice and inhibited cellular Th2 cytokines upon BLG restimulation. Since pre-existing humoral immunity inhibited the therapeutic effect of our glyco-polymerized BLG, we introduced a co-therapy (anti-CD20) to blunt the humoral response and observed ameliorated anaphylactic responses following glyco-polymerized BLG therapy. This platform may provide a potential T cell-modulating strategy to prevent and treat food allergies. This work was supported in part by seed funding from the Chicago Immunoengineering Innovation Center at the University of Chicago as well as the Food Allergy Fund.