Vaccines and adjuvants in allergen specific immunotherapy: current status and future directions

Allergen specific immunotherapy (AIT) has a history spanning over 110 years and represents the only disease-modifying treatment for allergic diseases, with potential preventive effects. Nevertheless, the broader application of AIT is limited by the inherent drawbacks of natural allergen extracts, such as variability in composition, risk of side effects, and complex, lengthy treatment regimens. Advances in molecular allergology have enabled the development of novel vaccine strategies—including recombinant allergens, hypoallergenic derivatives, allergen-derived peptides, and nucleic acid-based vaccines—that aim to improve safety, efficacy, and precision. However, no molecule-based AIT product has yet achieved regulatory approval, largely due to technical and clinical trial challenges. In parallel, immunomodulatory adjuvants such as monophosphoryl lipid A, CpG oligodeoxynucleotides, flagellin and mannan have demonstrated promising properties. These innovations have the potential to enhance AIT outcomes by promoting immune tolerance, reducing IgE responses, and improving patient compliance. This review summarizes the current landscape of allergen vaccines and adjuvant technologies under investigation for AIT, highlighting key advances, clinical data, and future directions aimed at overcoming existing limitations and optimizing treatment strategies for allergic diseases.