Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses.
Abstract: Insect-bite hypersensitivity (IBH) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type-I/type-IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin-5 (IL-5) is the key cytokine for eosinophils and we have previously shown that targeting IL-5 by vaccination reduces disease symptoms in horses. Here, we analyzed the potential for long-term therapy by assessing a second follow-up year of the previously published study. The vaccine consisted of equine IL-5 (eIL-5) covalently linked to a cucumber mosaic virus-like particle (VLP) containing a universal T cell epitope (CuMVTT ) using a semi-crossover design to follow vaccinated horses during a second treatment season. Thirty Icelandic horses were immunized with 300 μg of eIL-5-CuMVTT without adjuvant. The vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti-eIL-5 auto-antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms. Yearly vaccination against IL-5 may be a long-term solution for the treatment of IBH and other eosinophil-mediated diseases in horses and other species including humans.
© 2018 The Authors. Allergy Published by John Wiley & Sons Ltd.
Publication Date: 2018-11-25 PubMed ID: 30402930PubMed Central: PMC6587569DOI: 10.1111/all.13659Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study examines the use of a vaccine against a type of cytokine known as Interleukin-5 (IL-5) as a long-term therapy for insect-bite hypersensitivity (IBH) in horses. The results indicated that vaccination significantly reduced disease symptoms by lowering eosinophil (types of white blood cells) levels and might be a potential solution to treating eosinophil-mediated diseases in both animals and humans.
Research Context
- IBH in horses is a chronic allergic condition resulting from insect bites. This results in itchy skin lesions caused by type-I and type-IV allergic reactions and increased infiltration of eosinophils into the skin.
- IL-5 is a cytokine that plays a key role in the functioning of eosinophils. Previous studies had shown that targeting IL-5 through vaccination can reduce symptoms of the disease.
- This study extended the previous research by examining the potential for long-term therapy, assessed through a second follow-up year of the prior study.
Research Method
- The vaccine used in the study was made from equine IL-5 covalently linked to a cucumber mosaic virus-like particle (VLP) with a universal T-cell epitope (CuMV). This combination was tested in a semi-crossover design in a second treatment season.
- The study involved thirty Icelandic horses who were given the vaccine without an adjuvant. Safety data was collected throughout the study.
Key Findings
- The vaccine did not raise any safety concerns, and it was well tolerated by all horses.
- All the horses developed reversible anti-eIL-5 auto-antibody titers after vaccination, with the mean eosinophil level being reduced compared to placebo treatment.
- This reduction contributed to a significant decrease in clinical lesion scores, signifying a marked improvement in disease symptoms. This improvement was more pronounced in the second year of vaccination compared to the first year, likely due to the more stable antibody titers induced by a single booster injection.
- These results showed that response to the vaccine could be maintained over two seasons, and the horses remained protected against the disease symptoms.
Conclusion
- The study concludes that yearly vaccination against IL-5 could potentially serve as a long-term solution for treating IBH and other eosinophil-mediated diseases in horses, as well as other species including humans.
Cite This Article
APA
Fettelschoss-Gabriel A, Fettelschoss V, Olomski F, Birkmann K, Thoms F, Bühler M, Kummer M, Zeltins A, Kündig TM, Bachmann MF.
(2018).
Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses.
Allergy, 74(3), 572-582.
https://doi.org/10.1111/all.13659 Publication
Researcher Affiliations
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zurich, Switzerland.
- Evax AG, Münchwilen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zurich, Switzerland.
- Evax AG, Münchwilen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zurich, Switzerland.
- Evax AG, Münchwilen, Switzerland.
- Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
- Faculty of Medicine, University of Zurich, Zurich, Switzerland.
- Thurlandpraxis, Niederuzwil, Switzerland.
- Thurlandpraxis, Niederuzwil, Switzerland.
- Latvian Biomedical Research & Study Centre, Riga, Latvia.
- Faculty of Medicine, University of Zurich, Zurich, Switzerland.
- Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
- RIA Immunology, Inselspital, University of Bern, Bern, Switzerland.
- The Jenner Institute, Nuffield Department of Medicine, The Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, UK.
MeSH Terms
- Allergens / chemistry
- Allergens / immunology
- Animals
- Eosinophils / immunology
- Eosinophils / metabolism
- Epitope Mapping
- Epitopes / chemistry
- Epitopes / immunology
- Horse Diseases / etiology
- Horse Diseases / therapy
- Horses
- Hypersensitivity / veterinary
- Immunization
- Immunoglobulin E / immunology
- Insect Bites and Stings / complications
- Interleukin-5 / chemistry
- Interleukin-5 / immunology
- Leukocyte Count
- Models, Molecular
- Protein Conformation
- Structure-Activity Relationship
- Vaccines, Virus-Like Particle / administration & dosage
- Vaccines, Virus-Like Particle / immunology
Grant Funding
- 25758.1 PFLS-LS / Commission for Technology and Innovation
- CRSII3_154490 / Swiss National Science Foundation
- Benchmark Vaccines Limited, UK.
Conflict of Interest Statement
AFG, VF, FT, KB, MB, MK, TMK, and MFB are involved in the development of active immunotherapies. The authors FO and AZ have no conflict of interests to disclose.
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