Allergy vaccine development using the birch pollen major allergen Bet v 1 as example

Allergy vaccine development using the birch pollen major allergen Bet v l as example Allergic diseases comprise a complex interplay between an allergen, the allergenic source, and the immune system. To understand the mechanisms responsible for the development of an allergic disease, a detailed understanding of all participating components is an absolute prerequisite. The search of inherent properties of allergens to initiate TH2 polarization has uncovered several mechanisms of allergenicity. By using the birch pollen major allergen Bet v 1 as paradigm, this review discusses intrinsic properties of allergenic molecules which can initiate the immunologic polarization. Bet v 1 was separated from the pollen, and subjected to detailed physico-chemical, structural, as well as immunological analyses. Findings thereof could guide the way to associate the structure of Bet v 1 with its allergenic behavior. The knowledge gathered on natural Bet v I was transferred to design the Bet v 1-fold variant BM4, which, due to the induced structural rearrangements, showed a dramatic reduction in Bet v 1-specific IgE binding. The altered structure further modified the cross-talk of BM4 with dendritic cells (DC) leading to an increased uptake of the fold-variant by this cell type. In combination with an altered processing of BM4 by DC-derived endo-/lysosomal proteases, the subsequent T-cell response against BM4 was boosted. In addition, TH polarization was shifted from an allergic TH2-dominated to a mixed TH1/TH2 response. The data gathered on BM4 encourage clinical application and might serve as a milestone for designing new vaccine candidates, especially because it points out possibilities on how to address the T cell compartment in vaccine design a yet unexplored terrain.