Single-dose AAV vector gene immunotherapy to treat food allergy

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School of Dental Medicine::Departmental Papers (Dental)
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skin sensitization; food allergy; chicken egg ovalbumin; adeno-associated vectors; regulatory T cells; B cellsliver tolerance; gene therapy; antigen-specific immunotherapy; single dose
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Miguel Gonzalez-Visiedo; Xin Li; Maite Munoz-Melero; Michael D. Kulis; Henry Daniell; David M. Markusic

Immunotherapies for patients with food allergy have shown some success in limiting allergic responses. However, these approaches require lengthy protocols with repeated allergen dosing and patients can relapse following discontinuation of treatment. The purpose of this study was to test if a single dose of an adeno-associated virus (AAV) vector can safely prevent and treat egg allergy in a mouse model. AAV vectors expressing ovalbumin (OVA) under an ubiquitous or liver-specific promoter were injected prior to or after epicutaneous sensitization with OVA. Mice treated with either AAV8-OVA vector were completely protected from allergy sensitization. These animals had a significant reduction in anaphylaxis mediated by a reduction in OVA-specific IgE titers. In mice with established OVA allergy, allergic responses were mitigated only in mice treated with an AAV8-OVA vector expressing OVA from an ubiquitous promoter. In conclusion, an AAV vector with a liver-specific promoter was more effective for allergy prevention, but higher OVA levels were necessary for reducing symptoms in preexisting allergy. Overall, our AAV gene immunotherapy resulted in an expansion of OVA-specific FoxP3+ CD4+ T cells, an increase in the regulatory cytokine IL-10, and a reduction in the IgE promoting cytokine IL-13.

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Molecular Therapy Methods & Clinical Development
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