Mechanisms underlying allergy vaccination with recombinant hypoallergenic allergen derivatives

Abstract

Hundred years ago therapeutic vaccination with allergen-containing extracts has been introduced as a clinically effective, disease-modifying, allergen-specific and long-lasting form of therapy for allergy, a hypersensitivity disease affecting more than 25% of the population. Today, the structures of most of the disease-causing allergens have been elucidated and recombinant hypoallergenic allergen derivatives with reduced allergenic activity have been engineered to reduce side effects during allergen-specific immunotherapy (SIT). These recombinant hypoallergens have been characterized in vitro, in experimental animal models and in clinical trials in allergic patients. This review provides a summary of the molecular, immunological and preclinical evaluation criteria applied for this new generation of allergy vaccines. Furthermore, we summarize the mechanisms underlying SIT with recombinant hypoallergens which are thought to be responsible for their therapeutic effect.

Fig. 1

Therapeutic effects of vaccination with hypoallergens mediated by blocking antibodies. (A) Vaccination with hypoallergens induces allergen-specific IgG antibodies, which inhibit IgE binding to the allergen. (B) Blocking IgG antibodies bind to the allergen and inhibit IgE-mediated effector cell degranulation, and hence the immediate allergic symptoms. They prevent the allergen-uptake by IgE via Fcε-receptors on antigen-presenting cells, the presentation of allergen-derived peptides to Th1 and Th2 cells, and thus the activation of allergen-specific T cells, which may reduce late phase allergic reactions. They also inhibit the activation of allergen-specific memory Bε cells and therefore the boost of allergen-specific IgE antibody responses. (MC, mast cell; APC, antigen presenting cell; Th, T helper cell, Bε, memory Bε cell; EO, eosinophil granulocyte.)