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Home / Equine Research Bank / J Allergy Clin Immunol / Treating insect-bite hypersensitivity in horses with active ...
The Journal of allergy and clinical immunology2018; 142(4); 1194-1205.e3; doi: 10.1016/j.jaci.2018.01.041

Treating insect-bite hypersensitivity in horses with active vaccination against IL-5.

Abstract: Insect-bite hypersensitivity is the most common allergic dermatitis in horses. Excoriated skin lesions are typical symptoms of this seasonal and refractory chronic disease. On a cellular level, the skin lesions are characterized by massive eosinophil infiltration caused by an underlying allergic response. To target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils. The vaccine consisted of eIL-5 covalently linked to a virus-like particle derived from cucumber mosaic virus containing the tetanus toxoid universal T-cell epitope tt830-843 (CMVTT). Thirty-four Icelandic horses were recruited and immunized with 400 μg of eIL-5-CMVTT formulated in PBS without adjuvant (19 horses) or PBS alone (15 horses). The vaccine was well tolerated and did not reveal any safety concerns but was able to induce anti-eIL-5 autoantibody titers in 17 of 19 horses. This resulted in a statistically significant reduction in clinical lesion scores when compared with previous season levels, as well as levels in placebo-treated horses. Protection required a minimal threshold of anti-eIL-5 antibodies. Clinical improvement by disease scoring showed that 47% and 21% of vaccinated horses reached 50% and 75% improvement, respectively. In the placebo group no horse reached 75% improvement, and only 13% reached 50% improvement. Our therapeutic vaccine inducing autoantibodies against self IL-5 brings biologics to horses, is the first successful immunotherapeutic approach targeting a chronic disease in horses, and might facilitate development of a similar vaccine against IL-5 in human subjects.
Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
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Publication Date: 2018-04-04 PubMed ID: 29627082DOI: 10.1016/j.jaci.2018.01.041Google Scholar: Lookup
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  • Clinical Trial
  • Veterinary
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research explores the use of an active vaccine against IL-5 to treat insect-bite hypersensitivity, the most common allergic skin condition in horses. The vaccine, developed consisting of IL-5 linked to a cucumber mosaic virus particle, not only induced anti-IL-5 antibodies in most horses but also significantly reduced hypersensitivity symptoms, showing promise as a novel immunotherapeutic approach.

Objective & Hypothesis

  • The researchers aimed to develop an active vaccine that targets IL-5, a crucial factor in the allergenic response manifested as hypersensitivity to insect bites in horses.
  • The crux of the hypothesis is that by inducing an immune response against IL-5, the allergic response could be mitigated, thus reducing the skin lesions characteristic of the hypersensitivity.

Methodology

  • The vaccine created for the study was made by covalently linking equine IL-5 (eIL-5) to a virus-like particle derived from the cucumber mosaic virus incorporating the universal T-cell epitope of tetanus toxoid.
  • Thirty-four Icelandic horses were enrolled in the study. The horses were then administered with either 400µg of the eIL-5-CMV vaccine in PBS without adjuvant or PBS alone, for comparison.

Results & Findings

  • No safety concerns were observed after administering the vaccine, signifying the vaccine’s tolerability.
  • The vaccine successfully induced anti-eIL-5 autoantibodies in 17 of the 19 horses that were administered the vaccine. This was a significant observation confirming that the vaccine triggers an immune response.
  • In horses who produced these autoantibodies, there was a significant reduction in the clinical scores of the skin lesions in comparison to levels from the previous season and from placebo-treated horses. This directly correlated the vaccine to a reduction in the symptoms of hypersensitivity.
  • The protection provided by the vaccine was dependent on a minimum threshold of anti-eIL-5 antibodies. The necessary concentration or level of these antibodies, however, was not elucidated.
  • By comparing disease scoring, it was found that the vaccine led to a 50% improvement in 47% of horses, and a 75% improvement in 21% of horses, while no such level of improvement was seen in horses given the placebo.

Implications & Conclusions

  • This study is the first to show a successful immunotherapeutic approach to battle a chronic disease in horses with the use of a therapeutic vaccine that induces autoantibodies against the horse’s IL-5.
  • Given the success of this approach in horses, it paves a potential avenue for the development of a similar vaccine to target IL-5 in humans, thereby extending the significance of this study beyond veterinary applications and into human medicine.

Cite This Article

APA
Fettelschoss-Gabriel A, Fettelschoss V, Thoms F, Giese C, Daniel M, Olomski F, Kamarachev J, Birkmann K, Bühler M, Kummer M, Zeltins A, Marti E, Kündig TM, Bachmann MF. (2018). Treating insect-bite hypersensitivity in horses with active vaccination against IL-5. J Allergy Clin Immunol, 142(4), 1194-1205.e3. https://doi.org/10.1016/j.jaci.2018.01.041

Publication

The Journal of allergy and clinical immunology
ISSN: 1097-6825
NlmUniqueID: 1275002
Country: United States
Language: English
Volume: 142
Issue: 4
Pages: 1194-1205.e3

Researcher Affiliations

Fettelschoss-Gabriel, Antonia
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland; Evax AG, Münchwilen, Switzerland. Electronic address: Antonia.gabriel@usz.ch.
Fettelschoss, Victoria
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland; Evax AG, Münchwilen, Switzerland.
Thoms, Franziska
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
Giese, Christoph
  • ETH Zurich, Institute of Molecular Biology & Biophysics, Zurich, Switzerland.
Daniel, Michelle
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
Olomski, Florian
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
Kamarachev, Jivko
  • Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Birkmann, Katharina
  • Thurlandpraxis, Niederuzwil, Switzerland.
Bühler, Maya
  • Thurlandpraxis, Niederuzwil, Switzerland.
Kummer, Martin
  • Thurlandpraxis, Niederuzwil, Switzerland.
Zeltins, Andris
  • Latvian Biomedical Research & Study Centre, Riga, Latvia.
Marti, Eliane
  • Department for Clinical Research VPH, Vetsuisse Faculty of the University of Bern, Clinical Immunology Group, Bern, Switzerland.
Kündig, Thomas M
  • Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Bachmann, Martin F
  • RIA Immunology, Inselspital, University of Bern, Bern, Switzerland; Jenner Institute, Nuffield Department of Medicine, Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, United Kingdom.

MeSH Terms

  • Animals
  • Autoantibodies / immunology
  • Ceratopogonidae / immunology
  • Cucumovirus
  • Horse Diseases / immunology
  • Horse Diseases / therapy
  • Horses / immunology
  • Hypersensitivity / immunology
  • Hypersensitivity / therapy
  • Hypersensitivity / veterinary
  • Immunoglobulin E / immunology
  • Insect Bites and Stings / immunology
  • Insect Bites and Stings / therapy
  • Insect Bites and Stings / veterinary
  • Interleukin-5 / immunology
  • Random Allocation
  • Vaccination / veterinary

Citations

This article has been cited 35 times.
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