Sabados, M. | Search bioRxiv

bioRxiv2023

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

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 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 cows milk allergy, treatment with glycosylation-modified {beta}- 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.

bioengineering↗

bioRxiv2022

Microbial metabolite butyrate-prodrug polymeric micelles promote gut health and treat food allergies

The microbiome modulates host immunity and aids in maintenance of tolerance in the gut, where microbial and food-derived antigens are abundant. Modern lifestyle practices, including diet and antibiotic use, have depleted beneficial taxa, specifically butyrate-producing Clostridia. This depletion is associated with the rising incidence of food allergy, inflammatory bowel diseases, and other noncommunicable chronic diseases. Although butyrate is known to play important roles in regulating gut immunity and maintaining epithelial barrier function, its clinical translation is challenging due to its offensive odor and quick absorption in the upper gut. Here, we have developed two polymeric micelle systems, one with a neutral charge (NtL-ButM) and one with a negative charge (Neg-ButM) that release butyrate from their polymeric core in different regions of the gastrointestinal tract when administered intragastrically to mice. We show that these butyrate-containing micelles, used in combination, restore a barrier-protective response in mice treated with either dextran sodium sulfate or antibiotics. Moreover, butyrate micelle treatment protects peanut-allergic dysbiotic mice from an anaphylactic reaction to peanut challenge and rescues their antibiotic-induced dysbiosis by increasing the abundance of Clostridium Cluster XIVa. Butyrate micelle treatment also reduces the severity of colitis in a murine model. By restoring microbial and mucosal homeostasis, these butyrate-prodrug polymeric micelles may function as a new, antigen-agnostic approach for the treatment of allergic and inflammatory disease.

bioengineering↗