Nanoparticulate CpG Immunotherapy in RAO- Affected Horses: Phase I and IIa Study

作者:Klier J*; Lehmann B; Fuchs S; Reese S; Hirschmann A; Coester C; Winter G; Gehlen H
来源:JOURNAL OF VETERINARY INTERNAL MEDICINE, 2015, 29(1): 286-293.
DOI:10.1111/jvim.12492

摘要

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. Objectives: 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. Animals and 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. Conclusion and Clinical Importance: 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.

  • 出版日期2015-2