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

Klier, John D.; Geis, Sabine; Steuer, J; Geh, Katharina J.; Reese, Sven; Fuchs, Sebastian; Mueller, Ralf S.; Winter, Gerhard; Gehlen, Heidrun

doi:10.1002/iid3.198

Cited by 20 publications

(39 citation statements)

References 59 publications

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“…New immunomodulatory agents have been investigated in both human and equine allergic (Th‐2) asthma. Recently, nonspecific CpG‐GNP (nanoparticle‐bound cytosine‐phosphate‐guanosine oligodeoxynucleotides) based immunotherapy was shown to provide an effective, allergen‐independent approach to treatment of horses with RAO . Briefly, CpG is recognized by Toll‐like receptors (TLR9), that are expressed in equine pulmonary neutrophils, macrophages, and epithelial cells .…”

Section: Response To Treatmentmentioning

confidence: 99%

Equine asthma: Integrative biologic relevance of a recently proposed nomenclature

Bond

Léguillette

Richard

et al. 2018

Veterinary Internal Medicne

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The term “equine asthma” has been proposed as a unifying descriptor of inflammatory airway disease (IAD), recurrent airway obstruction (RAO), and summer pasture‐associated obstructive airway disease. Whilst the term will increase comprehensibility for both the lay and scientific communities, its biologic relevance must be compared and contrasted to asthma in human medicine, recognizing the limited availability of peer‐reviewed equine‐derived data, which are largely restricted to clinical signs, measures of airway obstruction and inflammation and response to therapy. Such limitations constrain meaningful comparisons with human asthma phenotypes. Suggested minimum inclusion criteria supporting the term asthma, as well as similarities and differences between IAD, RAO, and multiple human asthma phenotypes are discussed. Furthermore, differences between phenotype and severity are described, and typical features for equine asthma subcategories are proposed. Based on shared features, we conclude that mild/moderate (IAD) and severe (RAO) equine asthma are biologically appropriate models for both allergic and non‐allergic human asthma, with RAO (severe equine asthma) also being an appropriate model for late‐onset asthma. With the development of new biologic treatments in humans and the application of more targeted therapeutic approaches in the horse, it would appear appropriate to further investigate the allergic (Th‐2) and non‐allergic (non‐Th‐2) phenotypes of equine asthma. Further research is required to more fully determine the potential clinical utility of phenotype classification.

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Section: Response To Treatmentmentioning

confidence: 99%

Equine asthma: Integrative biologic relevance of a recently proposed nomenclature

Bond

Léguillette

Richard

et al. 2018

Veterinary Internal Medicne

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“…In comparison to the preceding studies considering the long‐term effect, the current study reveals that 10 inhalations resulted in medium to high clinical effects on 100% of the parameters upon 8 weeks after the final treatment (Table S5). Seven inhalations showed middle to high clinical effects on 80% of the measured values upon 6 weeks after treatment. In the study, in which the patients received five CpG inhalations,middle to high clinical effects were measured in 50% of the parameters 4 weeks after the final treatment.…”

Section: Discussionmentioning

confidence: 93%

“…18 GNPs have proven to be a safe and effective carrier system for the CpG inhalations. 15,16,19,20,22 Through variations in the production of the GNP, the previous production process could be optimized and designed more efficiently. 21 Based on the results of Zillies et al, 39 Geh et al also developed a storage stable and sterilised lyophilisate of the CpG-GNP dispersion, which in future will make its storage and application much easier and more practicable.…”

Section: Discussionmentioning

confidence: 99%

“…15,16,21 For the CpG-GNP single dose, each inhalation utilized 187.5 μg CpG-ODN, bound to 3.75 mg GNP and dispersed in 2.5 mL highly purified water (HPW), with a final concentration of 1.5 mg/mL GNP and 0.075 mg/mL CpG-ODN as described previously. 15,16,22 For the CpG-GNP double dose, each inhalation utilized 375 μg CpG-ODN, bound to 7.5 mg GNP and dispersed in 5 mL HPW with a final concentration of 1.5 mg/mL GNP and 0.075 mg/mL CpG-ODN. All inhalation treatments (CpG and beclomethasone) were administered via the Equine Haler (Equine HealthCare Aps, Hoersholm, Denmark) combined with the Aeroneb Go micropump nebulizer (Aerogen, Galway, Ireland) as described previously.…”

Section: Interventionmentioning

confidence: 99%

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Immunomodulatory asthma therapy in the equine animal model: A dose‐response study and evaluation of a long‐term effect

Klier

Bartl

Geuder

et al. 2019

Immunity Inflam & Disease

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Introduction Equine asthma represents a naturally occurring animal model for human allergic neutrophilic asthma. Inhalative nanoparticle‐bound cytosine‐phosphate‐guanosine (CpG‐GNP) immunotherapy, independent of specific allergens, has already shown promising clinical and immunological results in previous studies and offers the possibility to treat the underlying cause of the disease. This study analyses the relationship between dose and response, and evaluates a possible long‐term effect. Methods In the prospective, randomised, double‐blind clinical field study, 29 horses suffering from equine asthma received 10 inhalation treatments with either 187.5 µg CpG‐GNP (CpG single dose [CpGsd]; n = 11), 375 µg CpG‐GNP double dose (CpG double dose [CpGdd]; n = 9) (q48h for 20 days) or 1600 µg beclomethasone (n = 9) (q24h for 10 days). Each horse was examined three times: before the treatment (I), immediately after the 10 inhalations (II), and 8 weeks after the final inhalation (III). The three groups were compared according to clinical and laboratory parameters. The study examined the sustainability of the long‐term effect of the treatment after 8 weeks, as well as the tolerability of the formula as a double dose. Results The CpGsd resulted in a significant improvement in 82% of the parameters, the CpGdd in 72%. In the long‐term evaluation, the CpGsd showed a significant improvement in 100% of the parameters in comparison to the initial values, the CpGdd in 67%. On the immunological level, the bronchoalveolar lavage revealed a significant reduction of IL‐4, IL‐8, and interferon‐γ. Conclusion Both CpG groups displayed significant improvements in clinical and laboratory parameters, especially regarding the long‐term effect of CpGsd. Doubling the CpG dose did not result in any improvement in comparison to the original single dose. On the immunological level, an anti‐inflammatory, as well as an immunomodulatory effect, apart from a Th2‐dominated immune response, could be observed. This immunomodulatory inhalation treatment could indicate a new possibility for human allergic asthma therapy.

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“…Other factors causing or conducive to disease include toxins and allergens ingested with food, as well as bacterial or viral infections. Present treatments include allergen avoidance, anti-allergic medications, and immunotherapy, known as desensitization (Klier et al, 2017). Allergen-specific immunotherapy (ASIT) involves the use of initially very small but gradually increasing amounts of allergen solutions, determined on the basis of blood tests or skin tests.…”

Section: Introductionmentioning

confidence: 99%

Assessment of serum allergenspecific IgE levels in horses from Siedlce County, Poland

Drywulska-Gierasimiuk

Górski

Andraszek

et al. 2020

Vet. stn. (Online)

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The aim of the present study was to determine the frequency of different allergies in horses from central Poland. Allergic diseases are common in horses all over the world. Common conditions that have been associated with immunoglobulin E (IgE)-mediated allergy in horses include insect bite hypersensitivity (IBH), urticaria and recurrent airway obstruction (RAO). A variety of serological assays are available to measure serum levels of allergen-specific IgE antibodies. They can provide supportive evidence for a diagnosis of equine allergic dermatitis associated with environmental allergens. This study was performed on clinically healthy, Polish noble half-breed horses. In this study, four groups of allergens were identified as commonly inducing allergic reactions: American house dust mites (D. farinae), cultivated plants (rape), English plantain (Plantago lanceolata) and biting midges (Culicoides nubeculosus). More than 50% of horses showed positive reactions to these groups of allergens. The factor that contributed most to allergy occurrence among horses was American house dust mites (D. farinae). In recent years, efforts have been made to identify new allergens and to better understand the specific pathogenesis of allergic diseases in animals. The development of allergic disease diagnostics has been facilitated by the availability of diagnostic methods along with enhanced awareness of allergic diseases in veterinary practice. Allergic disorders in horses are ultimately gaining the attention they deserve thanks to the fact that veterinary allergology has become a dedicated veterinary discipline.

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

Cited by 20 publications

References 59 publications

Equine asthma: Integrative biologic relevance of a recently proposed nomenclature

Equine asthma: Integrative biologic relevance of a recently proposed nomenclature

Immunomodulatory asthma therapy in the equine animal model: A dose‐response study and evaluation of a long‐term effect

Assessment of serum allergenspecific IgE levels in horses from Siedlce County, Poland

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