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


CONCLUSIONS
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-gamma 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.
Schöll
I
I
Department of Pathophysiology, University of Vienna, Austria.
Weissenböck
A
A
Förster-Waldl
E
E
Untersmayr
E
E
Walter
F
F
Willheim
M
M
Boltz-Nitulescu
G
G
Scheiner
O
O
Gabor
F
F
Jensen-Jarolim
E
E
D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000818:Animals; D000906:Antibodies / Q000097:blood; D052179:Antigens, Plant; D001673:Biodegradation, Environmental; D003888:Desensitization, Immunologic / Q000379:methods*; D005260:Female; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007074:Immunoglobulin G / Q000097:blood; D019344:Lactic Acid; D051379:Mice; D008807:Mice, Inbred BALB C; D043942:Nanotubes; D010940:Plant Proteins / Q000008:administration & dosage* / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
D000485:Allergens; D000906:Antibodies; D052179:Antigens, Plant; D007074:Immunoglobulin G; D010940:Plant Proteins; D011108:Polymers; C061312:Bet v 1 allergen, Betula; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid