Allergen‐specific immunosuppression by mucosal treatment with recombinant Ves v 5, a major allergen of Vespula vulgaris venom, in a murine model of wasp venom allergy
- 27 October 2003
- journal article
- Published by Wiley in Immunology
- Vol. 110 (3), 376-385
- https://doi.org/10.1046/j.1365-2567.2003.01751.x
Abstract
Up to 5% of the population suffer from systemic, 19% from local allergic hypersensitivity reactions to stinging insects. Even though specific immunotherapy is very effective in treating allergy to insect venom, new concepts of treatment strategies with only the disease eliciting allergen in recombinant form, along with antigen application via a less invasive route might be suggested for enhanced treatment efficacy and compliance. In the present study we aimed (i) to establish a mouse model of wasp venom allergy, mimicking the natural mode of sensitization, and (ii) to develop a prophylactic treatment strategy based on mucosal tolerance induction, using one major wasp venom allergen in recombinant form, i.e. recombinant (r)Ves v 5. Immunization with wasp venom--with or without the use of the adjuvant aluminium hydroxide--led to comparable T helper 2-like immune responses in vivo and in vitro. Intranasal administration of rVes v 5 prior to sensitization with wasp venom resulted in a significant reduction of wasp venom-specific antibody levels (immunoglobulin E (IgE)/IgG2a), type I hypersensitivity reactions in vivo and cytokine production in vitro. Pretreatment with the whole venom was less effective and caused toxic side reactions in higher concentrations, suggesting a favourable use of the recombinant venom allergen for mucosal application. Increased mRNA levels of transforming growth factor-beta and interleukin-10, along with adoptive cell transfer experiments indicated that the immunosuppression after intranasal rVes v 5-application has been mediated by regulatory mechanisms. This is further supported by the fact that the immunosuppression to rVes v 5 was associated with a bystander suppression to the unrelated aero-allergen Bet v 1. In conclusion, we demonstrated that the intranasal application of recombinant Ves v 5 prevented subsequent allergic sensitization to all components of the whole wasp venom. As allergy to insect venom develops in dependence of the frequency of insect stings, a prophylactic treatment based on mucosal tolerance induction with recombinant allergens might be of interest for people at high risk to frequent exposure to the stinging insects.Keywords
This publication has 49 references indexed in Scilit:
- IL‐10 and TGF‐β cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapyEuropean Journal of Immunology, 2003
- Recombinant allergens: the future of the liagnosis and treatment of atopic allergyAllergy, 1998
- Induction of Tolerance via the Respiratory MucosaInternational Archives of Allergy and Immunology, 1998
- Allergens in Hymenoptera venom XXV: The amino acid sequences of antigen 5 molecules and the structural basis of antigenic cross-reactivityJournal of Allergy and Clinical Immunology, 1993
- Venom immunotherapy: 10 years of experience with administration of single venoms and 50 μg maintenance dosesJournal of Allergy and Clinical Immunology, 1992
- Antigen-driven bystander suppression after oral administration of antigens.The Journal of Experimental Medicine, 1991
- Hymenoptera venom-specific IgE antibodies in post-mortem sera from victims of sudden, unexpected deathClinical and Experimental Allergy, 1988
- Antigenic cross-reactivity of venom proteins from hornets, wasps, and yellow jacketsJournal of Allergy and Clinical Immunology, 1985
- Allergenic Components of Bald-Faced Hornet (V. maculata) VenomInternational Archives of Allergy and Immunology, 1985
- Studies of coexisting honeybee and vespid-venom sensitivityJournal of Allergy and Clinical Immunology, 1984