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Glycopolymer-conjugated antigens as an inverse vaccine platform prevent anaphylaxis in a pre-clinical model of food allergy

Cao, S;Maulloo, C;Raczy, M;Sabados, M;Slezak, A;Nguyen, M;Solanki, A;Wallace, R;Shim, H;Wilson, D;Hubbell, J;

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 an inverse vaccine technology that utilizes glycopolymer-conjugated antigens to induce antigen-specific non-responsiveness. The glycopolymer conjugates were administered intravenously (i.v.) or subcutaneously (s.c.) and were found to traffic to the liver or lymph nodes, respectively, leading to preferential internalization by antigen-presenting cells, educating the immune system to respond in an innocuous way. In a mouse model of cow’s milk allergy, treatment with glycopolymer-conjugated β-lactoglobulin (BLG) was effective in preventing the onset of allergy. In addition, s.c. administration of glycopolymer-conjugated BLG showed superior safety and potential in treating existing allergies in combination with an anti-CD20 co-therapy. This platform may provide an antigen-specific immunomodulatory strategy to prevent and treat food allergies.