title: 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 strategy for peanut-specific immunotherapy in human subjects.
authors.affiliation: Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY; Jaffe Food Allergy Institute, New York, NY.
authors.forename: Kamal D
authors.initials: KD
authors.lastname: Srivastava
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Conn.
authors.forename: Alyssa
authors.initials: A
authors.lastname: Siefert
authors.affiliation: Department of Biomedical Engineering, Yale University, New Haven, Conn; Department of Immunobiology, Yale University School of Medicine, New Haven, Conn.
authors.forename: Tarek M
authors.initials: TM
authors.lastname: Fahmy
authors.affiliation: Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Conn.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caplan
authors.affiliation: Pediatric Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, NY; Jaffe Food Allergy Institute, New York, NY.
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
authors.affiliation: Pediatric 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.
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Sampson
mesh_terms: D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D000818:Animals; D010367:Arachis / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood / Q000378:metabolism; D003888:Desensitization, Immunologic / Q000379:methods; D004195:Disease Models, Animal; D005260:Female; D006632:Histamine / Q000097:blood; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D019344:Lactic Acid; D051379:Mice; D053758:Nanoparticles; D021183:Peanut Hypersensitivity / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D010936:Plant Extracts / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
chemical_list: D000485:Allergens; D016207:Cytokines; D007074:Immunoglobulin G; D010936:Plant Extracts; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007073:Immunoglobulin E; D006632:Histamine
keywords: IgE; Peanut allergy; anaphylaxis; immunotherapy; mice; nanoparticle