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

2004; Wiley; Volume: 34; Issue: 2 Linguagem: Inglês

10.1111/j.1365-2222.2004.01884.x

1365-2222

Isabella Pali‐Schöll, Andrea Weissenböck, Elisabeth Förster‐Waldl, Eva Untersmayr, Franziska Roth‐Walter, Martin Willheim, G Boltz-Nitulescu, Otto Scheiner, Franz Gabor, Erika Jensen‐Jarolim,

Food Allergy and Anaphylaxis Research

Summary 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.