Next-Generation Allergen-Specific Immunotherapy for Food Allergy

Allergen-specific immunotherapy (AIT) is currently the only disease-modifying treatment for food allergies. The most extensively studied form of AIT is oral immunotherapy, in which an increasing dose of specific food allergen is gradually introduced to allergic patients for immune system "re-education." It has been demonstrated to effectively achieve desensitization, raising the threshold for inducing allergic reactions after allergen ingestion. However, lengthy dosing schedules and the occurrence of severe adverse events have impeded the adoption and compliance of oral immunotherapy. In recent years, extensive efforts in developing novel platforms have been directed to heighten the immunogenicity and lower the allergenicity of AIT, in hopes of increasing its efficacy and safety. Certain vaccine candidates have been investigated in preclinical and clinical trials. In this review, we aim to summarize the state-of-the-art technology of next-generation AIT vaccines for food allergy and explore research gaps in the field that warrant further investigation. We adopted a 'Cargo-Truck-Lubricant' analogy to illustrate the components of AIT, corresponding to modified allergens, carriers delivering the allergens, and the immunomodulators fostering the delivery. While most studies focused mainly on peanut allergy, novel AITs for other food allergies were still in preclinical stages. Future directions point towards optimization and the clinical translation of next-generation AIT vaccines to maximize the therapeutic outcome and minimize risks.