Intranasal tolerance induction with polypeptides derived from 3 noncross-reactive major aeroallergens prevents allergic polysensitization in mice

Background: Specific immunotherapy is less effective in patients with multiple allergic sensitizations compared with monosensitized patients. Objective: We therefore established a mouse model of polysensitization to the major birch and timothy grass pollen allergens to test whether allergic polysensitization can be prevented by multiple allergen application via the mucosal route. Methods: Female BALB/c mice were immunized intraperitoneally with recombinant (r) Bet v 1, rPhl p 1, and rPhl p 5. For intranasal tolerance induction, a mixture of the complete allergens was compared with allergen-derived immunodominant peptides applied either as a mixture or as a synthetic hybrid peptide composed of the T-cell epitopes of the 3 allergens. Results: Intranasal application of the mixture of the complete allergen molecules did not prevent polysensitization to the same allergens. In contrast, pretreatment with a mixture of the immunodominant peptides or the hybrid peptide led to significantly reduced allergen-specific IgE responses in sera, IL-4 production in vitro, and suppressed airway inflammation. TGF-beta mRNA levels did not change, and IL-10 production was significantly suppressed after the pretreatment. The fact that the reduction of IL-10 was not abrogated after IL-10 receptor neutralization and that tolerance was not transferable with splenocytes indicates that the suppression of T(H)2 responses in polysensitized mice might not be mediated by immunosuppressive cytokines. Conclusion: Our study demonstrates that it is possible to suppress allergic immune responses simultaneously to several clinical important allergens. Thus, mucosal coapplication of selected peptides/hybrid peptides could be the basis of a mucosal polyvalent vaccine to prevent multiple sensitivities in atopic patients.