Introduction
The cashew plant (Anacardium occidentale ) is a tropical evergreen tree belonging to the Anacardiaceae family, which includes mango and pistachio. It produces cashew seeds (nuts) that are regularly consumed by most of the world’s population. Unfortunately, cashew is also classified as one of the most potent allergenic food, and no approved specific treatment is available to address this issue.1 The prevalence of cashew allergy has risen over the last decades in industrial countries with the increasing consumption of this nut.2,3 Besides the prevalence, a high medical need for a treatment is warranted by the unique severity of anaphylactic reactions triggered by the consumption of cashew-containing food in allergic individuals.4,5 Consequently, safe treatments minimizing contact between cashew allergens and anaphylaxis-triggering effector cells, such as mast-cells, should be given paramount considerations. Investigational epicutaneous immunotherapy (EPIT) is under review by the U.S. FDA for peanut allergy treatment in children.6 This epicutaneous system is comprised of an allergen-adsorbed patch, held above the intact skin by a circular crown of adhesive foam to create an occlusive condensation chamber (Viaskin). This technology permits allergen solubilization by transepidermal water loss and promotes its delivery across the stratum corneum to epidermal Langerhans cells.7 This route of administration is a key element of the safety profile of EPIT, making it a relevant approach for the treatment of life-threatening allergies such as cashew.8 In that context, the aim of the present work was to assess the capacity of EPIT to protect against anaphylaxis in a mouse model of cashew allergy. To that end, a mouse model of IgE-mediated cashew anaphylaxis was first developed. Then, the ability of patches to deliver cashew allergens to skin dendritic cells was demonstrated. Finally, cashew-sensitized mice were treated with cashew patches (EPIT) for up to 16 weeks to measure the kinetic induction of specific antibodies and the level of protection afforded against anaphylaxis following oral challenge. Results showed that EPIT was able to significantly increase the level of cashew specific IgG2a (mouse equivalent of human IgG1) all along the therapy period. More importantly, EPIT mice were significantly protected against anaphylactic symptoms following oral challenge. Interestingly, this protection was associated with a strong decrease in the activation of mast-cells, which are the main immune effectors involved in IgE-mediated anaphylaxis.