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One step closer to immunotherapy for peanut allergy

Published online: September 13, 2019

Peanut allergy is one of the most common and severe IgE-mediated food allergies. Strict avoidance of this life-threatening food is the only risk-minimizing option currently available for peanut allergic patients. In contrast to its successful application in the treatment of inhalant allergies, allergen specific subcutaneous immunotherapy of peanut allergy is not yet available. Previous trials using either peanut extract or modified, hypoallergenic extracts or allergenic components as vaccines were stopped due to severe side effects or low efficacy. Other routes of application such as oral, sublingual or epicutaneous are still in development and require further confirmation of their safety and sustained efficacy.

In an article by Tscheppe and colleagues in The Journal of Allergy and Clinical Immunology (JACI) promising data were published that provide a basis for a potential new allergen-specific immunotherapy based on an Ara h 2 hypoallergen. Ara h 2 is the most potent of the 16 allergenic proteins hitherto identified in peanut. Variants of Ara h 2 were produced by either destroying linear (sequential), conformational (structure-dependent) or both types of IgE binding sites. The authors used these Ara h 2 variants to test a large cohort of peanut-allergic children and adults in order to characterize the individual patterns of IgE responses to Ara h 2. Based on the performance of the Ara h 2 variants, the authors designed a potential new vaccine component to be used for allergen-specific immunotherapy. Finally, the ability of this Ara h 2 hypoallergen to induce anaphylaxis in a mouse model of peanut allergy was evaluated.

Peanut-allergic patients reacted to Ara h 2 in a patient specific manner, displaying various patterns of IgE recognition. Allergen specific IgE from most patients bound to both linear and conformational epitopes of Ara h 2. The Ara h 2 variant in which both types of IgE binding sites had been removed was hypoallergenic for most patients. It did not bind IgE and showed a highly reduced ability to activate basophils. In contrast, the hypoallergen retained its ability to stimulate allergen specific T cells, a property that is a prerequisite of potential vaccine components meant for being used in immunotherapy. Peanut allergic mice challenged with the protein did not have anaphylactic reactions.

The fact that both types of IgE epitopes had to be destroyed in order to produce a hypoallergen that did not cause anaphylaxis may explain why previous immunotherapies that were based on hypoallergens that had either linear or conformational IgE binding sites modified failed. Future studies are needed to demonstrate whether this new hypoallergen is safe and effective in desensitizing peanut allergic mice and whether these results can be translated into clinical studies in humans.

The Journal of Allergy and Clinical Immunology (JACI) is the official scientific journal of the AAAAI, and is the most-cited journal in the field of allergy and clinical immunology.