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J Allergy Clin Immunol. 2016 Aug;138(2):536-543.e4. doi: 10.1016/j.jaci.2016.01.047. Epub 2016 Apr 26.

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

Author information

  • 1Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY; Jaffe Food Allergy Institute, New York, NY.
  • 2Department of Biomedical Engineering, Yale University, New Haven, Conn.
  • 3Department of Biomedical Engineering, Yale University, New Haven, Conn; Department of Immunobiology, Yale University School of Medicine, New Haven, Conn.
  • 4Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Conn.
  • 5Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY; Jaffe Food Allergy Institute, New York, NY. Electronic address: hugh.sampson@mssm.edu.

Abstract

BACKGROUND:

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.

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

Preclinical findings indicate that peanut oral immunotherapy with CpG/PN-NPs might be a valuable strategy for peanut-specific immunotherapy in human subjects.

KEYWORDS:

IgE; Peanut allergy; anaphylaxis; immunotherapy; mice; nanoparticle

PMID:
27130858
DOI:
10.1016/j.jaci.2016.01.047
[PubMed - in process]
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