title: Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study.
abstract: BACKGROUND
  Recurrent airway obstruction (RAO), an asthma-like disease, is 1 of the most common allergic diseases in horses in the northern hemisphere. Hypersensitivity reactions to environmental antigens cause an allergic inflammatory response in the equine airways. Cytosine-phosphate-guanosine-oligodeoxynucleotides (CpG-ODN) are known to direct the immune system toward a Th1-pathway, and away from the pro-allergic Th2-line (Th2/Th1-shift). Gelatin nanoparticles (GNPs) are biocompatible and biodegradable immunological inert drug delivery systems that protect CpG-ODN against nuclease degeneration. Preliminary studies on the inhalation of GNP-bound CpG-ODN in RAO-affected horses have shown promising results.
  
  
  OBJECTIVE
  The aim of this study was to evaluate the clinical and immunological effects of GNP-bound CpG-ODN in a double-blinded, placebo-controlled, prospective, randomized clinical trial and to verify a sustained effect post-treatment.
  
  
  METHODS
  Twenty-four RAO-affected horses received 1 inhalation every 2 days for 5 consecutive administrations. Horses were examined for clinical, endoscopic, cytological, and blood biochemical variables before the inhalation regimen (I), immediately afterwards (II), and 4 weeks post-treatment (III).
  
  
  RESULTS
  At time points I and II, administration of treatment rather than placebo corresponded to a statistically significant decrease in respiratory effort, nasal discharge, tracheal secretion, and viscosity, AaDO2 and neutrophil percentage, and an increase in arterial oxygen pressure.
  
  
  CONCLUSIONS
  Administration of a GNP-bound CpG-ODN formulation caused a potent and persistent effect on allergic and inflammatory-induced clinical variables in RAO-affected horses. This treatment, therefore, provides an innovative, promising, and well-tolerated strategy beyond conventional symptomatic long-term therapy and could serve as a model for asthma treatment in humans.
authors.affiliation: Centre for Clinical Veterinary Medicine, Equine Clinic, Ludwig Maximilians University, Munich, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Klier
authors.forename: B
authors.initials: B
authors.lastname: Lehmann
authors.forename: S
authors.initials: S
authors.lastname: Fuchs
authors.forename: S
authors.initials: S
authors.lastname: Reese
authors.forename: A
authors.initials: A
authors.lastname: Hirschmann
authors.forename: C
authors.initials: C
authors.lastname: Coester
authors.forename: G
authors.initials: G
authors.lastname: Winter
authors.forename: H
authors.initials: H
authors.lastname: Gehlen
mesh_terms: D000818:Animals; D001314:Auscultation; D005260:Female; D006734:Horse Diseases / Q000188:drug therapy*; D006736:Horses; D008168:Lung / Q000473:pathology; D008173:Lung Diseases, Obstructive / Q000188:drug therapy / Q000662:veterinary*; D008297:Male; D009093:Mucus; D053758:Nanoparticles / Q000009:adverse effects / Q000627:therapeutic use*; D009838:Oligodeoxyribonucleotides / Q000009:adverse effects / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D012119:Respiration / Q000187:drug effects
chemical_list: D009838:Oligodeoxyribonucleotides; D010100:Oxygen
keywords: Gelatin nanoparticle; Immunotherapy; Inhalation; RAO