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Glycosylation-modified antigens as a tolerance-inducing vaccine platform prevent anaphylaxis in a pre-clinical model of food allergy

Cao, S;Maulloo, CD;Raczy, MM;Sabados, M;Slezak, AJ;Nguyen, M;Solanki, A;Wallace, RP;Shim, HN;Wilson, DS;Hubbell, JA;

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 develop a toleranceinducing vaccine technology that utilizes glycosylation-modified antigens to induce antigen-specific nonresponsiveness. The glycosylation-modified antigens are administered intravenously (i.v.) or subcutaneously
(s.c.) and traffic to the liver or lymph nodes, respectively, leading to preferential internalization by antigenpresenting cells, educating the immune system to respond in an innocuous way. In a mouse model of
cow’s milk allergy, treatment with glycosylation-modified b-lactoglobulin (BLG) is effective in preventing
the onset of allergy. In addition, s.c. administration of glycosylation-modified BLG shows superior safety
and potential in treating existing allergies in combination with anti-CD20 co-therapy. This platform provides
an antigen-specific immunomodulatory strategy to prevent and treat food allergies.