title: Immunotherapy with a ragweed-toll-like receptor 9 agonist vaccine for allergic rhinitis.
abstract: BACKGROUND
  Conjugating immunostimulatory sequences of DNA to specific allergens offers a new approach to allergen immunotherapy that reduces acute allergic responses.
  
  
  METHODS
  We conducted a randomized, double-blind, placebo-controlled phase 2 trial of a vaccine consisting of Amb a 1, a ragweed-pollen antigen, conjugated to a phosphorothioate oligodeoxyribonucleotide immunostimulatory sequence of DNA (AIC) in 25 adults who were allergic to ragweed. Patients received six weekly injections of the AIC or placebo vaccine before the first ragweed season and were monitored during the next two ragweed seasons.
  
  
  RESULTS
  There was no pattern of vaccine-associated systemic reactions or clinically significant laboratory abnormalities. AIC did not alter the primary end point, the vascular permeability response (measured by the albumin level in nasal-lavage fluid) to nasal provocation. During the first ragweed season, the AIC group had better peak-season rhinitis scores on the visual-analogue scale (P=0.006), peak-season daily nasal symptom diary scores (P=0.02), and midseason overall quality-of-life scores (P=0.05) than the placebo group. AIC induced a transient increase in Amb a 1-specific IgG antibody but suppressed the seasonal increase in Amb a 1-specific IgE antibody. A reduction in the number of interleukin-4-positive basophils in AIC-treated patients correlated with lower rhinitis visual-analogue scores (r=0.49, P=0.03). Clinical benefits of AIC were again observed in the subsequent ragweed season, with improvements over placebo in peak-season rhinitis visual-analogue scores (P=0.02) and peak-season daily nasal symptom diary scores (P=0.02). The seasonal specific IgE antibody response was again suppressed, with no significant change in IgE antibody titer during the ragweed season (P=0.19).
  
  
  CONCLUSIONS
  In this pilot study, a 6-week regimen of the AIC vaccine appeared to offer long-term clinical efficacy in the treatment of ragweed allergic rhinitis. (ClinicalTrials.gov number, NCT00346086 [ClinicalTrials.gov] .).
authors.affiliation: Department of Medicine, Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, USA. pcretic@jhmi.edu
authors.forename: Peter S
authors.initials: PS
authors.lastname: Creticos
authors.forename: John T
authors.initials: JT
authors.lastname: Schroeder
authors.forename: Robert G
authors.initials: RG
authors.lastname: Hamilton
authors.forename: Susan L
authors.initials: SL
authors.lastname: Balcer-Whaley
authors.forename: Arouna P
authors.initials: AP
authors.lastname: Khattignavong
authors.forename: Robert
authors.initials: R
authors.lastname: Lindblad
authors.forename: Henry
authors.initials: H
authors.lastname: Li
authors.forename: Robert
authors.initials: R
authors.lastname: Coffman
authors.forename: Vicki
authors.initials: V
authors.lastname: Seyfert
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eiden
authors.forename: David
authors.initials: D
authors.lastname: Broide
mesh_terms: D000328:Adult; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology*; D031164:Ambrosia / Q000009:adverse effects / Q000276:immunology*; D052179:Antigens, Plant; D004311:Double-Blind Method; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D016233:Immunotherapy, Active / Q000009:adverse effects; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage / Q000276:immunology; D010865:Pilot Projects; D010940:Plant Proteins / Q000008:administration & dosage / Q000276:immunology*; D011058:Pollen / Q000276:immunology; D006255:Rhinitis, Allergic, Seasonal / Q000276:immunology / Q000628:therapy*; D012882:Skin Tests; D051217:Toll-Like Receptor 9 / Q000819:agonists*
chemical_list: D000485:Allergens; C026967:Amb a I protein, Ambrosia artemisiifolia; D052179:Antigens, Plant; D009838:Oligodeoxyribonucleotides; D010940:Plant Proteins; D051217:Toll-Like Receptor 9; D007073:Immunoglobulin E