Allergens and Adjuvants in Allergen Immunotherapy for Immune Activation, Tolerance, and Resilience

Allergen immunotherapy (AIT) is the only setting in which a vaccine is applied in patients allergic exactly to the active principle in the vaccine. Therefore, AIT products need to be not only effective but also safe. In Europe, for subcutaneous AIT, this has been achieved by the allergoid strategy in which IgE epitopes are destroyed or masked. In addition, adjuvants physically precipitate the allergen at the injection site to prevent too rapid systemic distribution. The choice of adjuvant critically shapes the efficacy and type of immune response to the injected allergen. In contrast to T_H2-promoting adjuvants, others clearly counteract allergy. Marketed products in Europe are formulated with aluminum hydroxide (alum) (66.7%), microcrystalline tyrosine (16.7%), calcium phosphate (11.1%), or the T_H1 adjuvant monophosphoryl lipid A (5.6%). In contrast to the European practice, in the United States mostly nonadjuvanted extracts and no allergoids are used for subcutaneous AIT, highlighting not only a regulatory but maybe a "historic preference." Sublingual AIT in the form of drops or tablets is currently applied worldwide without adjuvants, usually with higher safety but lower patient adherence than subcutaneous AIT. This article will discuss how AIT and adjuvants modulate the immune response in the treated patient toward immune activation, modulation, or-with new developments in the pipeline-immune resilience.