Intravenous immunotherapy with Der p 1-containing nanoparticles alleviates the allergic responses in a murine allergic rhinitis model.

Abstract

Subcutaneous immunotherapy has several limitations, including the long dose escalation period, frequent injections and risk of adverse reactions. Crude extracts used for immunotherapy can contain unrecognized immunostimulatory components or induce neosensitization. Therefore, in this study, we aimed to develop a new efficient method to induce allergen-specific immune tolerance using Dermatophagoides pteronyssinus (Der p) 1-containing nanoparticles. We developed two different types of allergen-containing poly(lactic-co-glycolic) [PLGA] nanoparticle vaccines: Der p 1-encapsulated and Der p 1-conjugated vaccines. House dust mite (HDM)-sensitized mice were administered positive control (PC), PLGA (vehicle control), encapsulated vaccine (EV), and conjugated vaccine (CV) via intravenous injections one week after sensitization. Subcutaneous immunotherapy group received three subcutaneous HDM extract injections at two-day intervals. After challenge, we compared the rhinitis symptoms, immunoglobulin (Ig) levels, and histopathology of the nasal mucosa and analyzed splenocyte cultures for cytokine production and regulatory T cell activation. EV and CV groups exhibited improved nasal symptoms and lower ear swelling and inflammation in the nasopharyngeal lavage and nasal tissues than PC group. Serum HDM-specific IgG1 levels were higher in EV and CV groups than in PC group. No changes were observed in the total and HDM-specific IgE levels in EV group. EV group exhibited lower interleukin-4, -5, -13, and -17 levels and higher interleukin-10 and interferon-γ levels than PC group. The two vaccinated groups exhibited significantly higher regulatory T cell activation than PC group. Overall, intravenously administered Der p 1-containing nanoparticles alleviated the allergic responses and induced tolerance in a murine allergic rhinitis model.