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

• DOI: 10.1101/2023.03.23.534004
• Publication Date: 2023-03-25T21:45:15Z
• Authors: Shijie Cao; Chitavi D. Maulloo; Michal M. Raczy; Matthew Sabados; Anna J. Slezak; Mindy Nguyen; Ani Solanki; Rachel P. Wallace; Ha-Na Shim; D. Scott Wilson; Jeffrey A. Hubbell
• Keywords: Mice; Vaccines; Glycosylation; Animals; Female; Cattle; Lactoglobulins; Milk Hypersensitivity; Anaphylaxis; Article; Food Hypersensitivity; 3. Good health

SummaryThe 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 tolerance-inducing vaccine technology that utilizes glycosylation-modified antigens to induce antigen-specific non-responsiveness. The glycosylation-modified antigens 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 glycosylation-modified β- lactoglobulin (BLG) was effective in preventing the onset of allergy. In addition, s.c. administration of glycosylation-modified 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.