Recombinant Probiotics for Allergen Immunotherapy

Currently, AIT represents the sole allergen-specific therapeutic approach dealing with IgE-mediated allergic disease able to control not only its symptoms, as other treatments do, but also to rebalance the immunological profile of allergic subjects. In fact, they develop detrimental immune responses towards allergens, exogenous proteins that should be otherwise harmless, entering the body from the external environment by feeding, breathing or by cutaneous absorption. The effectiveness of AIT is based on its immunological mechanisms which are complex and still not completely clarified. In this scenario, a central role seems to be played by the antigen presenting cells (APCs), typically dendritic cells (DCs) and macrophages [1]. They are induced by the AIT to mature into a phenotype able to guide differentiation of naïve T lymphocytes (TH0) into T helper type-1 (TH1) or T regulatory (Treg) cells [1]. The APCs promote these latter effects by activating two alternative cytokine patterns, IL-2 and IL-12 in the first case and IL-10 in the second. In turn, TH1 cells produce IFN-γ which prompt the immunoglobulin (Ig) isotype switch towards the production of allergen-specific IgG4 (IgG2 in mice), that compete with IgE for the binding to the allergen. The cytokines produced by Treg (IL-10 and TGF-β ) exert an inhibitory activity inducing energy or apoptosis of TH2 cells. In this way, they suppress the production of their characteristic cytokine IL4, which represents the main input for B lymphocytes to produce IgE. As a result, basophils and eosinophils cannot be activated to release mediators of the allergic inflammation which, as it is well known, fuel and amplify pre-existing immunological response and associated symptoms. In addition, the IgE-mediated antigen presentation by APCs and the stimulation of specific TH2 clones are inhibited. All these immunological variations counteract the allergic responses and contribute to restore the non-pathological ones towards exogenous proteins. The ultimate effects are desensitization and attenuation, or even complete disappearance, of allergic symptoms. However, the AIT, which involves the administration of an allergen in native form, could trigger anaphylaxis, in particular when high doses are necessary for an improved clinical outcome. Hence, AIT could be ameliorated in terms of safety and efficacy by developing hypoallergenic antigens [2-5], or adjuvant molecules [6-9] able to stimulate Treg