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Allergy2020; 75(4); 862-871; doi: 10.1111/all.14145

Interleukin 31 in insect bite hypersensitivity-Alleviating clinical symptoms by active vaccination against itch.

Abstract: Insect bite hypersensitivity (IBH) is the most common seasonal pruritic allergic dermatitis of horses occurring upon insect bites. In recent years, a major role for IL-31 in allergic pruritus of humans, monkeys, dogs, and mice was acknowledged. Here, we investigate the role of IL-31 in IBH of horses and developed a therapeutic vaccine against equine IL-31 (eIL-31). IL-31 levels were quantified in allergen-stimulated peripheral blood mononuclear cells (PBMCs) and skin punch biopsies of IBH lesions and healthy skin from IBH-affected and healthy horses. The vaccine consisted of eIL-31 covalently coupled to a virus-like particle (VLP) derived from cucumber mosaic virus containing a tetanus toxoid universal T-cell epitope (CuMVTT). Eighteen IBH-affected horses were recruited and immunized with 300 μg of eIL-31-CuMVTT vaccine or placebo and IBH severity score was recorded. IL-31 was increased in PBMCs and exclusively detectable in skin lesions of IBH-affected horses. Vaccination against eIL-31 reduced delta clinical scores when compared to previous untreated IBH season of the same horses and to placebo-treated horses in the same year. The vaccine was well tolerated without safety concerns throughout the study. TH2-derived IL-31 is involved in IBH pathology and accordingly the immunotherapeutic vaccination approach targeting IL-31 alleviated clinical scores in affected horses.
Publication Date: 2020-02-06 PubMed ID: 31816097PubMed Central: PMC7217000DOI: 10.1111/all.14145Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research article focuses on understanding the role of Interleukin 31 (IL-31) in insect bite hypersensitivity (IBH) among horses and developing a therapeutic vaccine against it. The study reveals that vaccination against IL-31 reduces the clinical symptoms related to IBH.

IL-31 and Its Role in Insect Bite Hypersensitivity

  • Insect Bite Hypersensitivity (IBH) is a seasonal allergic reaction seen in horses, primarily caused by insect bites. IL-31, a type of cytokine or protein that mediates immunity responses, is identified to have a significant role in this allergic reaction.
  • Previous research has acknowledged the role of IL-31 in allergic reactions and associated itching in humans, monkeys, dogs, and mice. However, its role in horses and specifically in IBH was not clear.
  • This research observes that IL-31 levels are increased in allergen-stimulated peripheral blood mononuclear cells (PBMCs) and in skin lesions of horses afflicted by IBH, thus suggesting its crucial role in the allergic reaction among horses.

Development of a Therapeutic Vaccine Against IL-31

  • Given the observed role of IL-31 in IBH, the researchers developed a vaccine targeting equine IL-31 (eIL-31). The vaccine was made up of eIL-31 that was covalently bonded to a virus-like particle (VLP) derived from the cucumber mosaic virus.
  • The VLP also contained a tetanus toxoid universal T-cell epitope (CuMVTT) for triggering the immune response.
  • A group of 18 horses affected by IBH was studied. Some of these horses were treated with the developed vaccine, while others were given a placebo.

Impact of the Vaccine on IL-31 and IBH

  • The researchers found that, compared to the horses’ previous untreated IBH season and the placebo-treated horses, those vaccinated against eIL-31 showed reduced clinical symptoms associated with IBH.
  • The vaccine was well-tolerated among the treated horses and there were no evident safety concerns throughout the study.
  • The outcome of the study suggests that IL-31 is an important player in IBH pathology and the vaccination strategy targeting IL-31 can be used to alleviate clinical symptoms in horses afflicted by IBH.

Cite This Article

APA
Olomski F, Fettelschoss V, Jonsdottir S, Birkmann K, Thoms F, Marti E, Bachmann MF, Kündig TM, Fettelschoss-Gabriel A. (2020). Interleukin 31 in insect bite hypersensitivity-Alleviating clinical symptoms by active vaccination against itch. Allergy, 75(4), 862-871. https://doi.org/10.1111/all.14145

Publication

ISSN: 1398-9995
NlmUniqueID: 7804028
Country: Denmark
Language: English
Volume: 75
Issue: 4
Pages: 862-871

Researcher Affiliations

Olomski, Florian
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Fettelschoss, Victoria
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zurich, Switzerland.
  • Evax AG, Münchwilen, Switzerland.
Jonsdottir, Sigridur
  • Department for Clinical Research VPH, Clinical Immunology Group, Vetsuisse Faculty of the University of Bern, Bern, Switzerland.
Birkmann, Katharina
  • Evax AG, Münchwilen, Switzerland.
Thoms, Franziska
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zurich, Switzerland.
Marti, Eliane
  • Department for Clinical Research VPH, Clinical Immunology Group, Vetsuisse Faculty of the University of Bern, Bern, Switzerland.
Bachmann, Martin F
  • RIA Immunology, Inselspital, University of Bern, Bern, Switzerland.
  • Nuffield Department of Medicine, The Jenner Institute, The Henry Wellcome Building for Molecular Physiology, University of Oxford, Oxford, UK.
Kündig, Thomas M
  • Faculty of Medicine, University of Zurich, Zurich, Switzerland.
  • Department of Dermatology, University Hospital Zurich, Zurich, Switzerland.
Fettelschoss-Gabriel, Antonia
  • Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland.
  • Faculty of Medicine, University of Zurich, Zurich, Switzerland.
  • Evax AG, Münchwilen, Switzerland.

MeSH Terms

  • Animals
  • Ceratopogonidae
  • Horses
  • Hypersensitivity / therapy
  • Insect Bites and Stings / complications
  • Interleukins
  • Leukocytes, Mononuclear
  • Pruritus
  • Vaccination

Conflict of Interest Statement

Dr Fettelschoss‐Gabriel reports grants from CTI during the conduct of the study, personal fees and nonfinancial support from Evax AG, during the conduct of the study; personal fees and non‐financial support from Evax AG, outside the submitted work; In addition, Dr Fettelschoss‐Gabriel has a patent WO 2017/042212 A1 licensed to Benchmark Animal Health Limited, and a patent WO 2018/162577 A1 pending. V Fettelschoss reports personal fees from Evax AG, during the conduct of the study and outside the submitted work; In addition, V Fettelschoss has a patent WO 2018/162577 A1 pending. Dr Thoms is an employee of HypoPet AG formerly Saiba Biotech GmbH. Dr Birkmann reports personal fees from Evax AG, outside the submitted work. Dr Bachmann reports personal fees from Evax AG, during the conduct of the study; personal fees and non‐financial support from Saiba GmbH, outside the submitted work; In addition, Dr Bachmann has a patent WO 2017/042212 A1 licensed to Benchmark Animal Health Limited, and a patent WO 2018/162577 A1 pending and MFB is an employee of the HypoPet AG formerly Saiba Biotech GmbH. Dr Kündig reports grants from CTI during the conduct of the study; personal fees from Evax AG, outside the submitted work. Dr Marti reports grants from Swiss National Science Foundation, grants from Morris Animal Foundation, grants from Stiftung Forschung für das Pferd, outside the submitted work. F Olomski has nothing to disclose. Dr Jonsdottir has nothing to disclose.

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Citations

This article has been cited 19 times.