Allergen-loaded biodegradable poly(D,L-lactic-co-glycolic) acid nanoparticles down-regulate an ongoing Th2 response in the BALB/c mouse model

Abstract

Background and objective: Biocompatible and biodegradable microparticles have gained interest as antigen delivery systems during the recent years. We investigated whether biodegradable poly(D,L-lactic-co-glycolic) acid (PLGA) nanospheres could be used as allergen vehicles for few-shot therapy of type I allergy. Methods: The major birch pollen allergen Bet v 1 was encapsulated in PLGA nanospheres (PLGA-Bet v 1). We examined the antigenicity and the immune response to PLGA-Bet v 1 in a BALB/c mouse model. Results: The antigenicity of Bet v 1 was largely unaffected by PLGA entrapment. When BALB/c mice were immunized subcutaneously with PLGA-Bet v 1, they formed allergen-specific IgG antibodies, but did not develop hypersensitivity to Bet v 1, as shown by type I skin tests. To evaluate their therapeutic potential, PLGA-Bet v 1 with or without Al(OH)3 or non-entrapped Bet v 1 with Al(OH)3 were used for single-shot treatment of sensitized mice. Both groups treated with PLGA-Bet v 1 developed high levels of Bet v 1-specific IgG2a antibodies (P<0.01), whereas IgG1 levels decreased significantly (P<0.01). Moreover, T cells from mice treated with PLGA-Bet v 1 showed IFN-γ and IL-10 production. The synthesis of these cytokines was enhanced in the groups where Al(OH)3 had been added to the vaccine formulation. Conclusion: Allergen-loaded PLGA nanoparticles modulate an ongoing Th2 response in the BALB/c mouse model, as demonstrated by down-regulation of IgG1 and production of IFN-γ and IL-10. Our data strongly suggest that PLGA nanospheres can advantageously be used for formulations of allergen extracts or allergen derivatives for the few-shot treatment of type I allergy.