Factors Influencing the Allergenicity and Adjuvanticity of Allergens

Stephan Deifl; Barbara Bohle

Disclosures

Immunotherapy. 2011;3(7):881-893. 

In This Article

Allergen–S-layer Fusion Proteins

S-layer proteins form crystalline arrays on the cell surface of many bacteria and most archaea and have already a long tradition in vaccine development.[104] Recombinant Bet v 1, the major birch pollen allergen, was fused with the S-layer protein from the nonpathogenic bacteria Geobacillus stearothermophilus ATCC 12980.[105] The resulting allergen–S-layer fusion protein induced IFN-γ and IL-10 production in PBMCs and Bet v 1-specific Th2 clones from birch pollen-allergic donors.[106] Moreover, the fusion protein displayed a reduced IgE-binding capacity and consequently a lower risk to induce adverse vaccine-related anaphylactic reactions. Similarly, a fusion protein consisting of Bet v 1 and a S-layer protein from Bacillus sphaericus CCM 2177 showed reduced IgE-binding and mediator-releasing capacity.[107] Because bacterial S-layer proteins target TLR2, allergen–S-layer fusion proteins induced DCs to mature and to synthesize IL-10 and IL-12.[108] DC maturation initiated by the fusion protein promoted the differentiation of naive CD4+ T cells into IFN-γ-producing cells in an IL-12-dependent manner. In parallel, a substantial number of naive T cells developed into IL-10-producing Treg cells that actively suppressed anti-CD3-stimulated T cells. Together, the fusion of an allergen and a bacterial danger signal endowed the allergen with intrinsic capacity to promote the induction of allergen-specific Th1 and Treg cells. In parallel, the IgE-binding capacity of the fusion protein was clearly reduced. The combined immunomodulatory activity and reduced IgE reactivity of allergen–S-layer fusion proteins makes them promising vaccine candidates for future SIT. Recently, allergen–S-layer fusion proteins were successfully expressed in Gram-positive bacteria, thereby facilitating their production as pyrogen-free active substances for allergy vaccines.[109]

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