A Nebulized Gelatin Nanoparticle-Based CpG Formulation is Effective in Immunotherapy of Allergic Horses

Klier, John D.; Fuchs, Sebastian; May, Anna; Schillinger, Ulrike; Plank, Christian; Winter, Gerhard; Coester, Conrad; Gehlen, Heidrun

doi:10.1007/s11095-012-0686-8

Cited by 46 publications

(75 citation statements)

References 28 publications

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“…As it has already been shown in vitro using equine BAL cells and in vivo , GNP‐bound CpG treatment stimulates upregulation of IL‐10 26, 32, 35. This cytokine, which among others is formed from Treg cells, has a regulatory effect on excessive pro‐inflammatory Th1 and pro‐allergic Th2 immune responses, as they occur in the lungs of RAO horses to various degrees 8.…”

Section: Discussionmentioning

confidence: 62%

“…No local or systemic inflammatory reactions were observed 26. The efficiency of this novel formulation was demonstrated by improvement in arterial blood gases, breathing rate, amount of intratracheal mucus accumulation, viscosity, and airway neutrophilia in RAO‐affected horses 26…”

mentioning

confidence: 95%

“…A preliminary study of the inhalation of GNP‐bound CpG‐ODN as the only active agent showed promising clinical results in a small group of RAO‐affected horses and healthy horses, in contrast to previously used adjuvants 26. No local or systemic inflammatory reactions were observed 26.…”

mentioning

confidence: 96%

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

Klier

Lehmann

Fuchs

et al. 2015

Veterinary Internal Medicne

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BackgroundRecurrent 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.ObjectivesThe 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 MethodsTwenty‐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).ResultsAt 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, AaDO 2 and neutrophil percentage, and an increase in arterial oxygen pressure.Conclusion and Clinical ImportanceAdministration 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.

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Section: Discussionmentioning

confidence: 62%

mentioning

confidence: 95%

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

Klier

Lehmann

Fuchs

et al. 2015

Veterinary Internal Medicne

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“…The clinical examination was conducted as previously reported 7, 8 and in accordance with established and standardized scoring systems 2, 14, 15, where available. The variables examined included the measurement of the following: breathing rate at rest, breathing type (relative units [RU] in the range of 0–4; where 0 = no or little movement in the ventral region of the flank, and 4 = obvious abdominal lift, heave line and nostril flaring) 14, nasal discharge (RU in the range of 0–3; 0 = none, 1 = mild, 2 = moderate, and 3 = severe discharge), auscultation of lungs and trachea (in the range of RU 0–4; 0 = physiological, 1 = mild, 2 = moderate, 3 = severe, 4 = wheezes/rhonchi) 2, 7, 8, and arterial blood gas parameters 15.…”

Section: Methodsmentioning

confidence: 99%

“…Furthermore, the absorption through endocytosis and thus the effect of the CpG is increased in the target cells 11. This delivery system is efficacious in‐vitro in BAL cells and in‐vivo in the horse 7, 8, 12.…”

Section: Introductionmentioning

confidence: 97%

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

Klier

Geis

Steuer

et al. 2017

Immunity Inflam & Disease

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IntroductionNew therapeutic strategies to modulate the immune response of human and equine allergic asthma are still under extensive investigation. Immunomodulating agents stimulating T‐regulatory cells offer new treatment options beyond conventional symptomatic treatment or specific immunotherapy for human and equine allergic airway diseases, with the goal of a homoeostatic T‐helper cell balance. The aim of this study was to evaluate the effects of a nebulized gelatin nanoparticle‐CpG formulation (CpG‐GNP) with and without specific allergens for the treatment of spontaneous allergic equine asthma as a model for human asthma.MethodsTwenty equine asthma‐affected horses were treated either with CpG‐GNP alone or CpG‐GNP with allergens. Two specific allergens were selected for each horse based on history and an in‐vitro test. Each horse received seven administrations of the respective nebulized composition and was examined before treatment, immediately after and 6 weeks after the treatment course.ResultsClinical parameters such as breathing rate, indirect interpleural measurement, arterial blood gases, amount of tracheal mucus and percentage of neutrophils and cytokines in tracheal washes and serum samples were evaluated. Treatment with CpG‐GNP alone as well as in combinations with relevant allergens resulted in clinical improvement of nasal discharge, breathing rate, amount of secretion and viscosity, neutrophil percentage and partial oxygen pressure directly after and 6 weeks after treatment. There were no significant differences between the two treatments in clinical parameters or local cytokine profiles in the tracheal wash fluid (IL‐10, IFN‐g, and IL‐17). IL‐4 concentrations decreased significantly in both groups.ConclusionNonspecific CpG‐GNP‐based immunotherapy shows potential as a treatment for equine and possibly also human allergic asthma.

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Recurrent Airway Obstruction and Inflammatory Airway Disease

Gerber

2013

Veterinary Allergy

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A Nebulized Gelatin Nanoparticle-Based CpG Formulation is Effective in Immunotherapy of Allergic Horses

Abstract: Thus this study, for the first time, showed effectiveness of colloidal nanocarrier-mediated immunotherapy in food-producing animals with potential future applicability to other species including humans.

Cited by 46 publications

References 28 publications

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

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

A comparison of nanoparticulate CpG immunotherapy with and without allergens in spontaneously equine asthma‐affected horses, an animal model

Recurrent Airway Obstruction and Inflammatory Airway Disease

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