title: Engineered recombinant peanut protein and heat-killed Listeria monocytogenes coadministration protects against peanut-induced anaphylaxis in a murine model.
abstract: Peanut allergy (PNA) is the major cause of fatal and near-fatal anaphylactic reactions to foods. Traditional immunotherapy using peanut (PN) protein is not an option for PNA therapy because of the high incidence of adverse reactions. We investigated the effects of s.c. injections of engineered (modified) recombinant PN proteins and heat-killed Listeria monocytogenes (HKLM) as an adjuvant on anaphylactic reactions in a mouse model of PN allergy. PN-allergic C3H/HeJ mice were treated s.c. with a mixture of the three major PN allergens and HKLM (modified (m)Ara h 1-3 plus HKLM). The effects on anaphylactic reactions following PN challenge and the association with Ab levels and cytokine profiles were determined. Although all mice in the sham-treated groups exhibited anaphylactic symptoms with a median symptom score of 3, only 31% of mice in the mAra h 1-3 plus HKLM group developed mild anaphylaxis, with a low median symptom score of 0.5. Alterations in core body temperature, bronchial constriction, plasma histamine, and PN-specific IgE levels were all significantly reduced. This protective effect was markedly more potent than in the mAra h 1-3 protein alone-treated group. HKLM alone did not have any protective effect. Reduced IL-5 and IL-13, and increased IFN-gamma levels were observed only in splenocytes cultures from mAra h 1-3 plus HKLM-treated mice. These results show that immunotherapy with modified PN proteins and HKLM is effective for treating PN allergy in this model, and may be a potential approach for treating PNA.
authors.affiliation: Department of Pediatrics, Mount Sinai School of Medicine, New York, NY 10029, USA. xiu-min.li@mssm.edu
authors.forename: Xiu-Min
authors.initials: XM
authors.lastname: Li
authors.forename: Kamal
authors.initials: K
authors.lastname: Srivastava
authors.forename: James W
authors.initials: JW
authors.lastname: Huleatt
authors.forename: Kim
authors.initials: K
authors.lastname: Bottomly
authors.forename: A Wesley
authors.initials: AW
authors.lastname: Burks
authors.forename: Hugh A
authors.initials: HA
authors.lastname: Sampson
mesh_terms: D055516:2S Albumins, Plant; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000627:therapeutic use; D000485:Allergens / Q000008:administration & dosage* / Q000627:therapeutic use; D000707:Anaphylaxis / Q000097:blood / Q000276:immunology / Q000517:prevention & control*; D000818:Animals; D052179:Antigens, Plant; D010367:Arachis / Q000009:adverse effects / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage* / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000276:immunology; D004359:Drug Therapy, Combination; D005260:Female; D005512:Food Hypersensitivity / Q000097:blood / Q000276:immunology / Q000517:prevention & control; D006023:Glycoproteins / Q000008:administration & dosage* / Q000627:therapeutic use; D006632:Histamine / Q000097:blood; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000627:therapeutic use; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007441:Intubation, Gastrointestinal; D008089:Listeria monocytogenes / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D008809:Mice, Inbred C3H; D010940:Plant Proteins / Q000008:administration & dosage* / Q000627:therapeutic use; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D055314:Seed Storage Proteins; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation / Q000276:immunology; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000627:therapeutic use
chemical_list: D055516:2S Albumins, Plant; D000276:Adjuvants, Immunologic; D000485:Allergens; D052179:Antigens, Plant; C500889:Ara h 1 protein, Arachis hypogaea; C078642:Ara h II protein, Arachis hypogaea; D001428:Bacterial Vaccines; D016207:Cytokines; D006023:Glycoproteins; D006633:Histamine Antagonists; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010940:Plant Proteins; D011994:Recombinant Proteins; D055314:Seed Storage Proteins; D014613:Vaccines, Attenuated; C118207:allergen Ara h3; D007073:Immunoglobulin E; D006632:Histamine