Bee Venom Immunotherapy: Current Status and Future Directions.

Bee venom immunotherapy is the main treatment option for bee sting allergy. Its major limitations are the high percentage of allergic side effects and long duration, which are driving the development of novel therapeutic modalities. Three general approaches have been evaluated including the use of hypoallergenic allergen derivatives, adjunctive therapy, and alternative delivery routes. This article reviews preclinical and clinical evidence on the therapeutic potential of these new therapies. Among hypoallergenic derivatives, hybrid allergens showed a markedly reduced IgE reactivity in mouse models. Whether they will offer therapeutic benefit over extract, it is still not known since clinical trials have not been carried out yet. T cell epitope peptides have proven effective in small clinical trials. Major histocompatibility complex class II restriction was circumvented by using long overlapping or promiscuous T cell epitope peptides. However, the T cell-mediated late-phase adverse events have been reported with both short and longer peptides. Application of mimotopes could potentially overcome both T cell- and IgE-mediated adverse events. During this evolution of vaccine, there has been a gain in safety. The efficacy was further improved with the use of Toll-like receptor-activating adjuvants and delivery systems. In murine models, the association of allergen Api m 1 with cytosine-guanosine rich oligonucleotides stimulated strong T-helper type-1 response, whereas its encapsulation into microbubbles protected mice against allergen challenge. An intralymphatic administration of low-dose vaccine has shown the potential to decrease treatment from 5 years to only 12 weeks. Bigger clinical trials are needed to follow up on these results.