https://www.jacionline.org/article/S0091-6749(19)31605-7/fulltext
The Journal of Allergy and Clinical Immunology, Published online: November 26, 2019. DOI: https://doi.org/10.1016/j.jaci.2019.11.022
Yang Yu, PhD, Mudnakudu Nagaraju Kiran Kumar, PhD, Mei X. Wu, PhD (Wellman Center for Photomedicine, Massachusetts General Hospital, Department of Dermatology, Harvard Medical School, Boston, MA, USA)
Background
More effective and safer immunotherapies to manage peanut allergy are in great demand despite extensive investigation of sublingual/oral (SLIT/OIT) and epicutaneous (EPIT) immunotherapies currently in the clinics.
Objective
To develop a powder-laden, dissolvable microneedle array (PLD-MNA) for epidermic delivery of powdered allergens and to evaluate efficacy of this novel EPIT in peanut-sensitized mice.
Methods
PLD-MNA was packaged with a mixture of powdered peanut allergen (PNA), vitamin-D3 (VD3), and CpG. Its epidermic delivery and therapeutic efficacy were evaluated, alongside PNA-specific Foxp3+T regulatory (Treg) cells and IL-10+ and TGF-β1+ skin-resident macrophages.
Results
PLD-MNA was successfully laden with PNA/VD3/CpG powder and capable to epidermically deliver most of its content one hour after applied onto intact mouse skin, concomitant with no significant leakage into the circulation or skin irritation. PLD-MNA-mediated EPIT substantially reduced clinical allergy scores to 1, from 3.5 in sham controls (p<0.001) after six treatments, accompanied with lower levels of PNA-specific IgE and intestinal mucosal mast cells and eosinophils over sham treatments. Moreover, in comparison with allergens intradermally administered, powdered allergens delivered by PLD-MNA preferentially attracted immunoregulatory macrophages and stimulated the cells to produce IL-10 and/or TGF-β at the immunization site, which may account for increased numbers of Treg-like cells in lymph tissues in association with systemic tolerance. PNA/VD3/CpG-laden PLD-MNA was safe and required only six treatments and one fifth of the PNA-adjuvant dose with improved outcomes, when compared to twelve conventional intradermal immunotherapies.
Conclusions
PLD-MNA holds great promise as a novel, safe, effective, and self-applicable modality to manage IgE-mediated allergies.
Keywords: epicutaneous immunotherapy (EPIT), tolerogenic adjuvant, powdered peanut allergens, immunoregulatory macrophages, dissolvable microneedle arrays, and T regulatory cells
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