Crushing peanuts From peanut allergy sensitization to innovative allergen immunotherapy strategies

Peanut allergy belongs to the group of most severe food allergies. Currently, there is only one active treatment for peanut allergy that has been approved by the FDA and EMA. This is an oral immunotherapy treatment that has been proven to be sufficiently safe and effective to induce desensitization, but treatment protocols can take up to three to five years, severe side-effects often occur, and there is a poor sustained efficacy. Therefore, innovative peanut AIT strategies are required, which we explored in this thesis. Multiple technologies have been studied, including modification of the major peanut allergen with sialic acid residues that could bind immune-inhibitory Siglec-9 receptors on antigen-presenting cells, as well as the use of particulates, such as liposomes and plant-based enveloped bioparticles (eBPs). The immune-modulating capacity of these innovative strategies was assessed in dendritic cells (DCs), CD4+ T cells, and allergenic effector cells such as mast cells and basophils. eBPs expressing ~3000 copies of Ara h 2 showed a 10.000- fold reduction in IgE binding potency compared to natural Ara h 2 and a similar degree of reduction in mast cell and basophil activation. Additionally, we demonstrated that they were immunogenic as they induced expression of maturation markers and production of cytokines on DCs, which polarized naïve CD4+ T cells towards Th1 cells, while simultaneously reducing Th2 development. These results mark Ara h 2 particulates as a novel peanut AIT therapy. Whether the use of one single peanut allergen is sufficient to induced effective T cell responses in vivo remains to be determined, as we have shown that Ara h 2 is differentially processed compared to the other major peanut allergens, which could reduce presentation of Ara h 2 peptides to T cells and could relate to the difficulty to detect Ara h 2-specific T cells in peanut allergic patient’s blood.