Allergen immunotherapy (AIT) is the only disease-modifying therapeutic approach for cat allergy, though it requires at least three years of treatment and can potentially induce severe systemic reactions. Plant-derived bioparticles expressing Fel d 1 allergen (Fel d 1 eBP) have been developed as a novel therapeutic candidate for cat allergy. Cellular and scRNA-seq analyses reveal that Fel d 1 eBP induce Th1 and IL-10 + T cells. We also demonstrate that Fel d 1 eBP targets the induction of protective metallothionine genes, CCL18 + monocytes and naïve B cells that are interferon responsive. Moreover, Fel d 1 eBP demonstrated reduced capacity to elicit basophil activation and histamine release, indicating their hypoallergenic nature. Administration of titrated doses of Fel d 1 eBP through skin prick test revealed that they are well-tolerated with reduced mean wheal compared to native Fel d 1 in open-label Phase 0 study. Altogether, we demonstrate that Fel d 1 eBP is hypo-allergenic and demonstrate tolerogenic properties making them a novel candidate for use in AIT for cat allergy.

Advances in molecular biology alongside the accelerated development of gene and cell engineering have contributed to the development of several endotype-targeted biological therapies against chronic immune-mediated allergic diseases. Conventional therapies for asthma, chronic rhinosinusitis with polyposis (CRSwNP), chronic spontaneous urticaria and atopic dermatitis (AD) are not without limitations, and as such the advent of biological therapies have provided a promising alternative treatment option. Biologicals have proven efficacious in the treatment of refractory chronic spontaneous urticaria, asthma, AD, CRSwNP and there is increasing evidence for their utility in treating food allergy. Biologicals are applied and investigated for the most urgent need: acute treatment, symptom control and reduction of steroid usage. Currently there are five approved biologicals for allergic disease management, targeted against IgE (omalizumab), type 2 (T2) cytokines and cytokine receptors (IL-4Ra; dupilumab, IL-5; mepolizumab/reslizumab, IL-5Ra; benralizumab).

Food allergy is an increasingly common disease worldwide, and is thought to be driven by an uncontrolled type 2 immune response. Current knowledge about the underlying mechanisms that initiate and promote an inappropriate immune response to dietary allergens is limited. Sensitization through the skin in early life is considered to be a key event. Food allergy results from a dysregulated type 2 response to food allergens, characterized by enhanced levels of IgE, IL-4, IL-5 and IL-13 with infiltration of mast cells, eosinophils and basophils during acute reactions. Recent data implies a possible role of innate lymphoid cells (ILCs) in driving food allergy. ILCs represent a group of lymphocytes that lack specific, recombined antigen receptors. They contribute to immune responses not only through the release of cytokines and other mediators, but also by responding to cytokines produced by activated cells in their local microenvironment. Due to their localization at barrier surfaces of the airways, gut and skin, ILCs form a link between the innate and adaptive immunity. This review summarizes recent evidences on how skin and gastrointestinal mucosal immune system contribute to both homeostasis and the development of food allergy, as well as the involvement of ILCs towards inflammatory processes and regulatory mechanisms.