Abstract
Allergen-specific immunotherapy (AIT) remains the only disease-modifying treatment for IgE-mediated allergy capable of inducing durable disease remission even after cessation of treatment. Conventional AIT delivered by subcutaneous injection is effective but requires long treatment courses and carries a risk of systemic reactions. Mucosal AIT strategies administered by oral, sublingual, or intranasal routes provide a safer, needle-free alternative, but are generally less immunogenic and hence less durable in their effects. Adjuvants have the potential to enhance the efficacy of AIT by improving antigen uptake, activating innate immune cells and/or by suppressing or redirecting pathogenic Th2 immune responses to allergens. This review synthesizes current evidence on how adjuvants might assist allergen immunotherapy, including by induction of regulatory T cells and regulatory B cells, augmentation of blocking IgG and IgA antibodies, and attenuation of IgE-driven effector responses. We survey major adjuvant classes and delivery platforms, including depot carriers, Toll-like receptor (TLR) agonists, nano-emulsions, liposomes, and polysaccharide-based nanoparticles, and summarize findings from preclinical models and early-phase clinical trials. Key translational challenges are considered, including issues of local and systemic safety, route-specific reactogenicity, manufacturing consistency, and regulatory evaluation. Finally, we outline design principles for next-generation adjuvanted AIT vaccines that aim for faster, safer, and more effective immunotherapy, with an emphasis on rational immune targeting and patient-centric delivery formats. Together, these insights highlight key design principles for adjuvanted allergen immunotherapies.