Modulation of allergic responses in mice by using biodegradable poly(lactide-co-glycolide) microspheres.
BACKGROUND
Biodegradable poly(lactide- co -glycolide) (PLGA) microspheres are a promising carrier for vaccine delivery capable of maturing antigen-presenting cells to stimulate T-cell-mediated immune responses. However, the potential of microspheres to downregulate an allergic response in vivo is unknown.


OBJECTIVE
The aim of this study was to determine whether microspheres could potentiate DNA vaccination against allergy and to evaluate the immunomodulatory properties of microspheres alone.


METHODS
Mice were treated prophylactically with DNA-loaded plain PLGA microspheres before sensitization with phospholipase A2 (PLA2), the major allergen of bee venom. PLA2-specific IgG1, IgG2a, IgE in serum were measured for 8.5 months, and splenocyte proliferative responses and cytokine profiles were determined. Protection against anaphylaxis was evaluated after injection of an otherwise lethal dose of PLA2.


RESULTS
Phospholipase A2-specific IgG1 and IgG2a production turned out to be 2 times higher using cationic microspheres compared with anionic microspheres, but was not influenced by the presence of DNA. In contrast, reduction in IgE production and T-cell hyporesponsiveness were observed with all microsphere formulations. Recall challenge with PLA2 triggered combined expression of both IL-4 and IFN-gamma, together with sustained expression of IL-10 that can explain the protective effect against anaphylaxis.


CONCLUSIONS
Our data suggest a dual mechanism that does initially rely on a TH2 to TH1 immune deviation and then on IL-10-mediated suppression. This is the first physiological demonstration that plain PLGA microspheres can induce tolerance in mice for as long as 6 months postsensitization.
Department of Chemistry and Applied BioSciences, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
Samantha
S
Jilek
Elke
E
Walter
Hans P
HP
Merkle
Blaise
B
Corthésy
D020341:Absorbable Implants; D000818:Animals; D001514:Bee Venoms / Q000276:immunology*; D001672:Biocompatible Materials / Q000008:administration & dosage; D004337:Drug Carriers; D006967:Hypersensitivity / Q000276:immunology / Q000628:therapy*; D007279:Injections, Subcutaneous; D016753:Interleukin-10 / Q000276:immunology; D051379:Mice; D008863:Microspheres; D023421:Models, Animal; D010741:Phospholipases A / Q000276:immunology; D054467:Phospholipases A2; D011098:Polyglactin 910 / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination / Q000295:instrumentation; D019444:Vaccines, DNA / Q000008:administration & dosage*
D001514:Bee Venoms; D001672:Biocompatible Materials; D004337:Drug Carriers; D019444:Vaccines, DNA; D016753:Interleukin-10; D011098:Polyglactin 910; D010741:Phospholipases A; D054467:Phospholipases A2