Recent developments and future strategies for immunotherapy of insect venom allergy

Hymenoptera venom allergy may cause life-threatening, sometimes even fatal, allergic reactions and thus may be associated with a serious reduction in the quality of life. Venom immunotherapy is effective in the majority of patients with this allergy. Treatment failures do however occur and immunotherapy may cause frequent systemic allergic side effects, especially in honeybee venom-allergic patients. New strategies to improve safety and efficacy of this treatment are therefore of general interest.

Among these new strategies are premedication with antihistamines: this definitely reduces side effects and based on recent in-vitro experiments and one clinical controlled study may even improve efficacy by modulating the T-cell response through interference with histamine receptors on these cells. Furthermore, during recent years the cDNA of most major allergens of bee and vespid venoms has been cloned and these allergens have been expressed in recombinant form. This allows for the preparation of patient-tailored extracts, with or without reduction of their allergenicity, for example by using unrefolded or point-mutated recombinant allergens. Yet another approach is the use of non IgE binding peptide fragments of the allergen with preserved T-cell epitopes for immunotherapy. Such preparations of bee venom phospholipase A2 have been used successfully in pilot studies. Finally, DNA vaccination with phospholipase A2 sequence plasmids has proved effective in one experimental study in sensitized mice.

A number of new strategies for venom immunotherapy, mostly based on genetic engineering, have been described and we await their use in clinical medicine.