Mannan‑, VLP-, and flagellin-based adjuvants for allergen-specific immunotherapy: a review of the current literature

Currently, allergen-specific immunotherapy (AIT) with active ingredients derived from the causative allergen source is the only disease-modifying treatment for allergic patients. However, compared to, e.g., live-attenuated vaccines for the prevention of infectious diseases, purified allergens for AIT in many cases display only a low immunogenicity. This reduces treatment efficacy and prolongs treatment duration. Here, adjuvants may be a promising tool, allowing for dose reduction of the respective allergen while increasing immunogenicity of co-applied allergens and/or modulating allergen-specific immune responses toward T helper 1 (Th1) or regulatory phenotypes or the production of blocking antibody isotypes. Currently available adjuvants can be distinguished into first-generation adjuvants (promoting immune responses via aggregation and controlled release of co-applied allergens from a depot) and second-generation adjuvants (triggering immune responses via the activation of pattern recognition receptors expressed by immune cells). This review summarizes the mechanisms and effects of adjuvants currently or previously used for AIT (aluminum hydroxide, calcium phosphate, microcrystalline tyrosine, and monophosphoryl lipid A [MPLA]) and focuses on novel developments using mannan-, virus-like particle (VLP)-, and flagellin-based adjuvants and therapeutics for the treatment of allergic diseases.