title: Development of a poly (lactic-co-glycolic acid) particle vaccine to protect against house dust mite induced allergy.
abstract: Poly(lactic-co-glycolic acid) (PLGA) particles carrying antigen and adjuvant is a promising vaccine system which has been shown to stimulate systemic antigen-specific immune responses. In this study, we investigated the relationship of (i) the sizes of PLGA particle and (ii) the presence of cytosine-phosphate-guanine motifs (CpG), with the extent and type of immune response stimulated against Dermatophagoides pteronyssinus-2 (Der p2) antigen. Different sizes of PLGA particles encapsulating CpG were prepared using a double emulsion solvent evaporation method. Mice were vaccinated with Der p2 and different sizes of empty or CpG-loaded PLGA particles. Vaccinated mice were exposed to daily intranasal instillation of Der p2 for 10 days followed by euthanization to estimate leukocyte accumulation in bronchoalveolar lavage (BAL) fluids, antibody profiles, and airway hyperresponsiveness. PLGA particles showed a size-dependent decrease in the proportion of eosinophils found in BAL fluids. Mice vaccinated with the Der p2 coated on 9-μm-sized empty PLGA particles showed increased levels of IgE and IgG1 antibodies as well as increased airway hyperresponsiveness. All sizes of PLGA particles encapsulating CpG prevented airway hyperresponsiveness after Der p2 exposures. Inflammatory responses to Der p2 exposure were significantly reduced when smaller PLGA particles were used for vaccination. In addition, encapsulating CpG in PLGA particles increased IgG2a secretion. This study shows that the size of PLGA particles used for vaccination plays a major role in the prevention of house dust mite-induced allergy and that incorporation of CpG into the PLGA particles preferentially develops a Th1-type immune response.
authors: Division of Pharmaceutics and Translational Therapeutics, College of Pharmacy, University of Iowa, Iowa City, Iowa, 52242, USA.
authors: Vijaya B
authors: VB
authors: Joshi
authors: Andrea
authors: A
authors: Adamcakova-Dodd
authors: Xuefang
authors: X
authors: Jing
authors: Amaraporn
authors: A
authors: Wongrakpanich
authors: Katherine N
authors: KN
authors: Gibson-Corley
authors: Peter S
authors: PS
authors: Thorne
authors: Aliasger K
authors: AK
authors: Salem
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*; D016535:Bronchial Hyperreactivity / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D002626:Chemistry, Pharmaceutical; D018899:CpG Islands; D004195:Disease Models, Animal; D004337:Drug Carriers; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry*; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000503:physiopathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D039981:Pyroglyphidae / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000097:blood / Q000276:immunology / Q000503:physiopathology / Q000517:prevention & control*; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D014611:Vaccination; D014612:Vaccines / Q000737:chemistry / Q000276:immunology / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D039741:Antigens, Dermatophagoides; C559662:Derp2 allergen, Dermatophagoides pteronyssinus; D004337:Drug Carriers; D007074:Immunoglobulin G; D014612:Vaccines; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007073:Immunoglobulin E