Abstract
Food allergy is a growing health concern worldwide. Current allergen-specific immunotherapy (AIT) approaches require frequent dosing over extended periods of time and may induce anaphylaxis due to allergen-effector cell interactions. A critical need remains to develop novel approaches that refine AIT for the treatment of food allergies. Previous studies show that poly(lactide-co-glycolide) (PLG) nanoscale particles (NP) effectively suppress Th1- and Th17-driven immune pathologies. However, their ability to suppress the distinct Th2-polarized immune responses driving food allergy are unknown. Herein, we describe the safety and efficacy of NPs containing encapsulated peanut allergen in desensitizing murine models of peanut allergy. Peanut extract encapsulation allowed for the safe intravenous delivery of allergen relative to non-encapsulated approaches. Application of 2–3 doses, without the need for dose escalation, was sufficient to achieve prophylactic and therapeutic efficacy, which correlated with suppression of Th2-mediated disease and reduced mast cell degranulation. Efficacy was associated with strong reductions in a broad panel of Th1, Th2, and Th17 cytokines. These results demonstrate the ability of PLG NPs to suppress allergen-specific immune responses to induce a more tolerogenic phenotype, conferring protection from intragastric allergen challenge. These promising studies represent a step forward in the development of improved immunotherapies for food allergy.
Highlights
The incidence of food allergy is increasing worldwide and currently affects ∼10% of the population in the US, or more than 30 million patients [1]
Mice were sensitized with peanut extract and alum and treated with nanoscale particles (NP) containing various amounts of peanut extract conjugated via carbodiimide chemistry to their surface (Figure 1A)
Increasing concentrations of peanut extract (PE) in PBS were injected intravenously to imitate the effects of burst release of allergen
Summary
The incidence of food allergy is increasing worldwide and currently affects ∼10% of the population in the US, or more than 30 million patients [1]. Masked Delivery of Allergen (EPIT), and sublingual (SLIT) immunotherapies representing potential routes of delivery [5]. These therapies can temporarily desensitize patients and, in some instances, may suppress Th2 responses through the induction of regulatory and Th1 responses [6]. 9.4% of patients taking Palforzia, an FDAapproved OIT for peanut allergy, had an anaphylactic reaction prior to reaching maintenance dose [11] while other OIT trials have more generally resulted in significant adverse events for 22–27% of enrolled children [14]. While OIT is beneficial for many patients and caregivers, technologies to induce allergenspecific tolerance safely, rapidly, effectively, and equitably remain a critical clinical need
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