D2.188 - Low allergenicity of food allergen by Galactomannan Conjugation and immunotherapeutic efficacy of peanut-galactomannan conjugate in a mouse model of peanut allergy

Although oral immunotherapy (OIT) is an emerging treatment option, its clinical use is limited by a heightened risk of anaphylaxis compared with traditional avoidance or placebo approaches. This safety concern, combined with the need for sustained desensitization, underscores the necessity for alternative strategies that offer effective yet safer treatment options for food allergies. In this study, we developed a food allergen conjugated with galactomannan using the Maillard reaction, a process that may reduce allergenicity by altering epitope structures through the introduction of sugar chains. 

The food allergen and galactomannan powders were mixed at a 1:9 weight ratio and subjected to dry-heating at 60°C under 65% relative humidity for 14 days. The allergenicity of food allergen-GM was assessed in vitro by immunoblotting, skin prick tests (SPT), and basophil activation tests (BAT) measuring CD203c expression. The therapeutic efficacy of peanut(PE)-GM was evaluated in a murine model of peanut allergy through intragastric administration for three weeks, followed by assessments of anaphylactic symptoms, hypothermia, and serum levels of mast cell degranulation marker mMCP-1. This clinical study was approved by the Research Ethics Committee of the Graduate School of Medicine, Chiba University, Japan (approval no. 2882). 

Food allergen-GM significantly reduced IgE binding compared to the unmodified food allergen, as confirmed by immunoblotting. Also, SPT responses were significantly reduced in food allergen-GM compared to the unmodified food allergen. BAT results revealed that the basophil activation was reduced in PE-GM compared to PE. In the mouse model, treatment with PE-GM resulted in markedly lower hypothermia and anaphylactic symptom scores, as well as reduced serum mMCP-1 levels compared with PE-sensitized control mice. 

In conclusion, this study confirmed the reduced allergenicity of food allergen-GM based on IgE binding, BAT, and SPT in food allergy patients, and demonstrated its efficacy for safer OIT in a mouse model of peanut allergy. We are currently conducting a clinical trial using PE-GM.