Investigation of peanut oral immunotherapy with CpG/peanut nanoparticles in a murine model of peanut allergy

Abstract

Treatments to reverse peanut allergy remain elusive. Current clinical approaches using peanut oral/sublingual immunotherapy are promising, but concerns about safety and long-term benefit remain a barrier to wide use. Improved methods of delivering peanut-specific immunotherapy are needed. We sought to investigate the efficacy and safety of peanut oral immunotherapy using CpG-coated poly(lactic-co-glycolic acid) nanoparticles containing peanut extract (CpG/PN-NPs) in a murine model of peanut allergy. C3H/HeJ mice were rendered peanut allergic by means of oral sensitization with peanut and cholera toxin. Mice were then subjected to 4 weekly gavages with CpG/PN-NPs, vehicle (PBS), nanoparticles alone, peanut alone, CpG nanoparticles, or peanut nanoparticles. Untreated mice served as naive controls. After completing therapy, mice underwent 5 monthly oral peanut challenges. Anaphylaxis was evaluated by means of visual assessment of symptom scores and measurement of body temperature and plasma histamine levels. Peanut-specific serum IgE, IgG1, and IgG2a levels were measured by using ELISA, as were cytokine recall responses in splenocyte cultures. Mice with peanut allergy treated with CpG/PN-NPs but not vehicle or other treatment components were significantly protected from anaphylaxis to all 5 oral peanut challenges, as indicated by lower symptom scores, less change in body temperature, and a lower increase of plasma histamine levels. Importantly, CpG/PN-NP treatment did not cause anaphylactic reactions. Treatment was associated with a sustained and significant decrease in peanut-specific IgE/IgG1 levels and an increase in peanut-specific IgG2a levels. Compared with vehicle control animals, peanut recall responses in splenocyte cultures from nanoparticle-treated mice showed significantly decreased levels of TH2 cytokines (IL-4, IL-5, and IL-13) but increased IFN-γ levels in cell supernatants. Preclinical findings indicate that peanut oral immunotherapy with CpG/PN-NPs might be a valuable strategyfor peanut-specific immunotherapy in human subjects.