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.
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.
Winkler
Birgit
B
Department of Pathophysiology, University of Vienna, Austria.
Bolwig
Caroline
C
Seppälä
Ulla
U
Spangfort
Michael D
MD
Ebner
Christof
C
Wiedermann
Ursula
U
D000485:Allergens / Q000627:therapeutic use*; D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000517:prevention & control*; D018928:Immunity, Mucosal; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007299:Insect Bites and Stings / Q000150:complications*; D051379:Mice; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000627:therapeutic use; D012882:Skin Tests; D013154:Spleen / Q000276:immunology; D014862:Wasp Venoms / Q000276:immunology*
D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D011994:Recombinant Proteins; C431905:Ves v 5 allergen; D014862:Wasp Venoms; D007073:Immunoglobulin E