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.