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Development of a poly (lactic-co-glycolic acid) particle vaccine to protect against house dust mite induced allergy
Journal article   Open access   Peer reviewed

Development of a poly (lactic-co-glycolic acid) particle vaccine to protect against house dust mite induced allergy

Vijaya B Joshi, Andrea Adamcakova-Dodd, Xuefang Jing, Amaraporn Wongrakpanich, Katherine N Gibson-Corley, Peter S Thorne and Aliasger K Salem
The AAPS journal, Vol.16(5), pp.975-985
09/2014
DOI: 10.1208/s12248-014-9624-5
PMCID: PMC4147059
PMID: 24981892
url
https://doi.org/10.1208/s12248-014-9624-5View
Published (Version of record) Open Access

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.
Adjuvants, Immunologic - pharmacology Bronchial Hyperreactivity - immunology Immunoglobulin G - blood Vaccination Male Antigens, Dermatophagoides - pharmacology Th1 Cells - immunology Immunoglobulin E - blood Bronchial Hyperreactivity - blood Drug Carriers Antigens, Dermatophagoides - immunology Vaccines - pharmacology Vaccines - chemistry Adjuvants, Immunologic - chemistry Bronchial Hyperreactivity - physiopathology Respiratory Hypersensitivity - prevention & control Respiratory Hypersensitivity - physiopathology Disease Models, Animal Th1 Cells - drug effects Lactic Acid - chemistry Solubility Vaccines - immunology Technology, Pharmaceutical - methods Lung - physiopathology Bronchial Hyperreactivity - prevention & control Respiratory Hypersensitivity - immunology Chemistry, Pharmaceutical Mice, Inbred C3H Particle Size Respiratory Hypersensitivity - blood Animals Lung - drug effects Polyglycolic Acid - chemistry CpG Islands Mice Kinetics Antigens, Dermatophagoides - chemistry Lung - immunology Pyroglyphidae - immunology

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