Intranasal tolerance induction with polypeptides derived from 3 noncross-reactive major aeroallergens prevents allergic polysensitization in mice
Received 9 July 2004; received in revised form 10 March 2005; accepted 1 April 2005. published online 24 May 2005.
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-β 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 TH2 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.
aFrom the Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna
bDepartment of Clinical Chemistry and Molecular Diagnostics, Hospital of the Philipps University Marburg
Reprint requests: Ursula Wiedermann, MD, PhD, Department of Specific Prophylaxis and Tropical Medicine, Center for Physiology and Pathophysiology, Medical University of Vienna, Kinderspitalgasse 15, A-1095 Vienna, Austria.
Supported by grants from the Austrian Science Fund (F01814, P14634-PAT, Y0784GEN, FWF T163).
ABSTRACT