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Microneedle-Mediated Allergen-Specific Immunotherapy for the Treatment of Airway Allergy in Mice

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journal contribution
posted on 23.07.2020, 18:37 by Akhilesh Kumar Shakya, Chang Hyun Lee, Harvinder Singh Gill
Subcutaneous allergen-specific immunotherapy (SCIT) qualifies as a promising approach for the permanent cure of IgE-mediated airway allergies, which can often manifest into allergic rhinitis and other allergic respiratory diseases. SCIT entails repeated administration of a high allergen dose into the subcutaneous (sc) region using a hypodermic needle for many (3–5) years, which is inconvenient and painful and reduces patient compliance. To overcome these limitations, we hypothesized that microneedles (MNs), which are minimally invasive and painless, could provide a novel approach for allergen desensitization by depositing the allergen into the superficial layers of the skin. To test this hypothesis, we compared MNs and SCIT for allergen desensitization in a mouse model of ovalbumin (Ova)-induced airway allergy. Mice were first made allergic to Ova and then treated with MNs coated with Ova (with or without CpG as an adjuvant) or via SCIT-Ova + alum (subcutaneous Ova + alum injections) for comparison. Treatment with coated MNs significantly induced Ova-specific serum IgG antibodies in a manner comparable to SCIT-Ova + alum-treated group. To test the efficacy against allergen challenge, treated mice were challenged with Ova via the nasal route. Coated MNs with Ova and CpG (MN-Ova + CpG) considerably suppressed the airway inflammation in allergic mice, evidenced by downregulation of proinflammatory cytokines (IL-5 and IL-13), upregulation of anti-inflammatory cytokine IL-10, and activation of Ova-specific immune response in bronchoalveolar (BAL) fluid. The therapeutic capacity of MN-based allergy treatment was further validated by the reduction in eosinophil and mast cell infiltration in the lung tissues of mice treated with MN-Ova + CpG, and low deposition of mucus inside their lung bronchioles. Overall, coated MNs ameliorated the symptoms of airway allergy in mice similar to SCIT and could provide a novel means of painless allergen-specific immunotherapy.