Vitamin D3 improves the effects of low dose Der p 2 allergoid treatment in Der p 2 sensitized Balb/c mice.

Airborne allergens can induce an immunological chronic disease characterized by airway hyperresponsiveness and inflammation, mediated by exaggerated Th2 immune response. Allergen-specific immunotherapy (AIT) is effective for treating this condition. Recently, 1α,25-dihydroxyvitamin D3 (VD3), the active metabolite of vitamin D3, was described to be a potent inducer of T regulatory cells. It is well known that these cells play a central role in effective AIT. If it is true that vitamin D3 can improve the effects of AIT it should also allow the reduction of the vaccine doses while preserving its positive effects. This would decrease the amount of allergen in human vaccines thereby lowering the cost of drugs, considered determinant (which is considered as a crucial/essential element for) for adherence to treatment. For this reason, the major purpose of the present study was to verify if a low dose of AIT associated to VD3 has similar effects to those of common AIT at usual doses. Allergoids are hypoallergenic derivatives of allergens characterized by reduced availability of IgE binding sites, while preserving epitopes necessary for T cell recognition and for induction of non pathogenic IgG blocking antibodies. Therefore, we investigated whether the co-administration of VD3 could potentiate the effect of AIT when added to a low dose of chemically-modified monomeric allergoid of Der p 2 (d2-OID), in a Derp p 2-sensitized BALB/c mice model. The d2-OID alone confirmed to be not fully successful. On the contrary, the co-treatment with VD3 and d2-OID induced reduction of airway eosinophilia and Th2 cytokines with concomitant increase of IL-10 in lung tissue and Der p 2-specific IgG2a in serum. Moreover, a new comparative experiment with the native (recombinant) d2+VD3 or d2-OID+VD3, the first treatment produced an anaphylactic reaction in 4 out of 10 mice and no improvement of the allergic inflammation, whereas the latter confirmed to be efficacious and lasting (10 weeks after first immunization).