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.