Development of a Poly (lactic-co-glycolic acid) Particle Vaccine to Protect Against House Dust Mite Induced Allergy

Abstract

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 cytosinephosphate-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.

Peptide/protein vaccine delivery system based on PLGA particles

“…81 Furthermore, small-sized PLGA particle in the presence of CpG can be useful for developing Th1-polarized immunity in asthmatic response induced by house dust mite (HDM) allergens. 82 PLGA functions more efficiently and demonstrates longer potency and fewer side effects as compared to the conventional Al(OH) 3 adjuvant. Therefore, PLGA-allergen nanoparticles can act suitably as candidates for allergy vaccines.…”

CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies

“…Joshi et al 91 encapsulated CpG-B ODNs in PLGA particles using the double emulsion solvent evaporation method, where the particles were separated into three average sizes of 300 nm, 1 μm, and 9.2 μm depending upon differences in the sedimentation conditions of the centrifugation. They investigated the therapeutic effect on house dust allergies based on the differences in the size of PLGA particles, when the surface of these particles was coated with the house dust mite allergen Der p2.…”

Nanoparticles in Vaccine Delivery

“…Although CPS-loaded albumin-based nanoparticles were found to induce expression of co-stimulatory molecules and acts as antigen depots, thereby sparing antigen dose, high doses of CPS lead to upregulation of CD95 resulting in decreased immunogenicity and decreased viability of antigen presenting cell populations. Finally, my research group reported on the development of a PLGA particle vaccine that can protect against house dust mite induced allergy [14]. Our study showed that the size of PLGA particles used for vaccination plays a major role in the prevention of house dust miteinduced allergy and that incorporation of CpG into the PLGA particles preferentially develops a Th1-type immune response.…”