title: A phase 1 study of heat/phenol-killed, E. coli-encapsulated, recombinant modified peanut proteins Ara h 1, Ara h 2, and Ara h 3 (EMP-123) for the treatment of peanut allergy.
abstract: BACKGROUND
  Immunotherapy for peanut allergy may be limited by the risk of adverse reactions.
  
  
  OBJECTIVE
  To investigate the safety and immunologic effects of a vaccine containing modified peanut proteins.
  
  
  METHODS
  This was a phase 1 trial of EMP-123, a rectally administered suspension of recombinant Ara h 1, Ara h 2, and Ara h 3, modified by amino acid substitutions at major IgE-binding epitopes, encapsulated in heat/phenol-killed E. coli. Five healthy adults were treated with 4 weekly escalating doses after which 10 peanut-allergic adults received weekly dose escalations over 10 weeks from 10 mcg to 3063 mcg, followed by three biweekly doses of 3063 mcg.
  
  
  RESULTS
  There were no significant adverse effects in the healthy volunteers. Of the 10 peanut-allergic subjects [4 with intermittent asthma, median peanut IgE 33.3 kUA /l (7.2-120.2), and median peanut skin prick test wheal 11.3 mm (6.5-18)]; four experienced no symptoms; one had mild rectal symptoms; and the remaining five experienced adverse reactions preventing completion of dosing. Two were categorized as mild, but the remaining three were more severe, including one moderate reaction and two anaphylactic reactions. Baseline peanut IgE was significantly higher in the five reactive subjects (median 82.4 vs 17.2 kUA /l, P = 0.032), as was baseline anti-Ara h 2 IgE (43.3 versus 8.3, P = 0.036). Peanut skin test titration and basophil activation (at a single dilution) were significantly reduced after treatment, but no significant changes were detected for total IgE, peanut IgE, or peanut IgG4.
  
  
  CONCLUSIONS
  Rectal administration of EMP-123 resulted in frequent adverse reactions, including severe allergic reactions in 20%.
authors.affiliation: Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. rwood@jhmi.edu
authors.forename: R A
authors.initials: RA
authors.lastname: Wood
authors.forename: S H
authors.initials: SH
authors.lastname: Sicherer
authors.forename: A W
authors.initials: AW
authors.lastname: Burks
authors.forename: A
authors.initials: A
authors.lastname: Grishin
authors.forename: A K
authors.initials: AK
authors.lastname: Henning
authors.forename: R
authors.initials: R
authors.lastname: Lindblad
authors.forename: D
authors.initials: D
authors.lastname: Stablein
authors.forename: H A
authors.initials: HA
authors.lastname: Sampson
mesh_terms: D055516:2S Albumins, Plant / Q000276:immunology / Q000627:therapeutic use*; D000285:Administration, Rectal; D000293:Adolescent; D000328:Adult; D000485:Allergens / Q000276:immunology / Q000627:therapeutic use*; D052179:Antigens, Plant / Q000276:immunology / Q000627:therapeutic use*; D003888:Desensitization, Immunologic / Q000379:methods*; D004926:Escherichia coli; D005260:Female; D006023:Glycoproteins / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008565:Membrane Proteins; D008875:Middle Aged; D021183:Peanut Hypersensitivity / Q000276:immunology / Q000628:therapy*; D010940:Plant Proteins / Q000276:immunology / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D055516:2S Albumins, Plant; D000485:Allergens; D052179:Antigens, Plant; C500889:Ara h 1 protein, Arachis hypogaea; C500890:Ara h 2 allergen, Arachis hypogaea; C549941:Ara h 3 allergen, Arachis hypogea; D006023:Glycoproteins; D008565:Membrane Proteins; D010940:Plant Proteins; D011994:Recombinant Proteins