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A1285 - Customizable Allergen Desensitization Using Biodegradable Microspheres Containing Th1 Allergen Epitopes
Author Block: S. Killingbeck1, A. Haczku2; 1School of Medicine, University of California Davis, Davis, CA, United States, 2Pulmonary, Critical Care and Sleep Medicine, University of California, Davis, Davis, CA, United States.
RATIONALE: Subcutaneous or oral allergen-specific immunotherapy using allergen encapsulated within biodegradable poly(D, L-lactic-co-glycolic) acid (PLGA) microspheres and CpG (Th1 adjuvant) has been shown in mice to significantly increase allergen-specific IgG2a antibodies and Th1 immunity compared to traditional treatment with allergen injection alone. It is thought that the sustained, slow release of protein from PLGA microspheres over time enhances activation of Th1 immunity and a return to allergen tolerance. In contrast, inhaled microsphere-based allergen desensitization has been characterized with antigen alone but not in conjuction with adjuvant. METHODS: We studied the effect of PLGA encapsulated OVA peptide + CpG and monophosphoryl Lipid A (MPLA, Th1 adjuvant) on two populations of lung-resident CD103+ and lung-infiltrating CD11b+ bone marrow derived-dendritic cells (BMDC) to develop a more effective and less-invasive route of allergen immunotherapy. Bone marrow cells from WT C57BL/6 mice were cultured with Flt3L and GM-CSF for 11 days, then treated with 2.5 µg/mL MPLA and 1 mg/mL PLGA microspheres encapsulating OVA + CpG or MPLA + OVA alone and co-cultured for an additional week. DCs were split into CD103+ and CD11b+ populations and activation was then assessed by flow cytometry, including MHC II, CCR7, CD86, and CCR4 expression. RESULTS: Microsphere-based delivery enhances CD11b+ and CD103+ DC activation and provides sustained release of allergenic proteins, decreasing the risk for anaphylaxis and lowering the number of administrations necessary to re-induce tolerance. Inhaled delivery of allergen-encapsulated PLGA microspheres provides the possibility of self-administration in allergic patients and targets directly the airway cells involved in inhaled allergy exacerbation. The synthetic nature of delivery system allows cost-efficient production and an ability to readily synthesize peptides to cater to patients’ allergen(s) and MHC haplotype. Further study is warranted to characterize inhaled PLGA microsphere-based allergen immunotherapy.