FREE SHIPPING over $40
OVER 10000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
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.
Get Full Text
Publication Date: 2018-04-04 PubMed ID: 29627082DOI: 10.1016/j.jaci.2018.01.041Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • 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.
  1. Minić-Pantić D, Abela B, Lehtimäki J, Zink A, Jensen-Jarolim E, Fettelschoss-Gabriel A, Traidl-Hoffmann C, Ring J, Schmid-Grendelmeir P, Prélaud P, Taïeb A. Examining Atopic Dermatitis Through the One Health Concept Lens. Allergy 2026 Feb;81(2):345-357.
    doi: 10.1111/all.70080pubmed: 41014009google scholar: lookup
  2. Jebbawi F, Olomski F, Inversini V, Keller G, Rhiner T, Waldern N, Lam J, Pantelyushin S, Canonica F, Birkmann K, Johansen P, Kündig TM, Fettelschoss-Gabriel A. Anti-IL-5 Vaccination Dampens Allergen-Specific IgE Levels and Modulates IL-4 and IL-5 Th2 Cytokines in Skin Allergy of Mice and Horses. Allergy 2025 Dec;80(12):3377-3390.
    doi: 10.1111/all.70020pubmed: 40838325google scholar: lookup
  3. Neukirch L, Uhrig-Schmidt S, von Werthern K, Tuch A, Kraske JA, Lyu Y, Lenoir B, Eichmüller SB, Meyer M, Zörnig I, Jäger D, Schmidt P. Neo-antigen tumor vaccination depends on CD4-licensing conveyed by adeno-associated virus like particles. Mol Ther 2025 Oct 1;33(10):5003-5016.
    doi: 10.1016/j.ymthe.2025.07.014pubmed: 40671675google scholar: lookup
  4. Prudhomme J, Bardet C, Rakotoarivony I, Garros C, Bouhsira É, Lienard E. Local investigation into the role of Culicoides species diversity (Diptera: Ceratopogonidae) in recurrent horse dermatitis cases in southwest France. Parasit Vectors 2025 Mar 5;18(1):86.
    doi: 10.1186/s13071-025-06694-2pubmed: 40045427google scholar: lookup
  5. Schwarz E, Jebbawi F, Keller G, Rhiner T, Fricker A, Waldern N, Canonica F, Schoster A, Fettelschoss-Gabriel A. Phenotypic Shift of an Inflammatory Eosinophil Subset into a Steady-State Resident Phenotype after 2 Years of Vaccination against IL-5 in Equine Insect Bite Hypersensitivity. Vet Sci 2024 Oct 5;11(10).
    doi: 10.3390/vetsci11100476pubmed: 39453068google scholar: lookup
  6. Graner A, Mueller RS, Geisler J, Bogenstätter D, White SJ, Jonsdottir S, Marti E. Allergen immunotherapy using recombinant Culicoides allergens improves clinical signs of equine insect bite hypersensitivity. Front Allergy 2024;5:1467245.
    doi: 10.3389/falgy.2024.1467245pubmed: 39403119google scholar: lookup
  7. Jebbawi F, Chemnitzer A, Dietrich M, Pantelyushin S, Lam J, Rhiner T, Keller G, Waldern N, Canonica F, Fettelschoss-Gabriel A. Cytokines and chemokines skin gene expression in correlation with immune cells in blood and severity in equine insect bite hypersensitivity. Front Immunol 2024;15:1414891.
    doi: 10.3389/fimmu.2024.1414891pubmed: 39076967google scholar: lookup
  8. Berreiros-Hortala H, Vilchez-Pinto G, Diaz-Perales A, Garrido-Arandia M, Tome-Amat J. Virus-like Particles as Vaccines for Allergen-Specific Therapy: An Overview of Current Developments. Int J Mol Sci 2024 Jul 6;25(13).
    doi: 10.3390/ijms25137429pubmed: 39000536google scholar: lookup
  9. Sobczak JM, Barkovska I, Balke I, Rothen DA, Mohsen MO, Skrastina D, Ogrina A, Martina B, Jansons J, Bogans J, Vogel M, Bachmann MF, Zeltins A. Identifying Key Drivers of Efficient B Cell Responses: On the Role of T Help, Antigen-Organization, and Toll-like Receptor Stimulation for Generating a Neutralizing Anti-Dengue Virus Response. Vaccines (Basel) 2024 Jun 14;12(6).
    doi: 10.3390/vaccines12060661pubmed: 38932390google scholar: lookup
  10. Birkmann K, Jebbawi F, Waldern N, Hug S, Inversini V, Keller G, Holm A, Grest P, Canonica F, Schmid-Grendelmeier P, Fettelschoss-Gabriel A. Eosinophils Play a Surprising Leading Role in Recurrent Urticaria in Horses. Vaccines (Basel) 2024 May 21;12(6).
    doi: 10.3390/vaccines12060562pubmed: 38932291google scholar: lookup
  11. Herrmann I, Sanchez AJ. Efficacy and Safety of Subcutaneous Allergen-Specific Immuno-Therapy in Horses with Allergic Cutaneous and Respiratory Diseases-A Systematic Review. Vet Sci 2023 Oct 10;10(10).
    doi: 10.3390/vetsci10100613pubmed: 37888565google scholar: lookup
  12. Cox A, Stewart AJ. Insect Bite Hypersensitivity in Horses: Causes, Diagnosis, Scoring and New Therapies. Animals (Basel) 2023 Aug 4;13(15).
    doi: 10.3390/ani13152514pubmed: 37570323google scholar: lookup
  13. Zhang J, Yang J, Li Q, Peng R, Fan S, Yi H, Lu Y, Peng Y, Yan H, Sun L, Lu J, Chen Z. T Cell Activating Thermostable Self-Assembly Nanoscaffold Tailored for Cellular Immunity Antigen Delivery. Adv Sci (Weinh) 2023 Sep;10(26):e2303049.
    doi: 10.1002/advs.202303049pubmed: 37395451google scholar: lookup
  14. Langreder N, Schäckermann D, Meier D, Becker M, Schubert M, Dübel S, Reinard T, Figge-Wegener S, Roßbach K, Bäumer W, Ladel S, Hust M. Development of an inhibiting antibody against equine interleukin 5 to treat insect bite hypersensitivity of horses. Sci Rep 2023 Mar 10;13(1):4029.
    doi: 10.1038/s41598-023-31173-ypubmed: 36899044google scholar: lookup
  15. Mohsen MO, Bachmann MF. Virus-like particle vaccinology, from bench to bedside. Cell Mol Immunol 2022 Sep;19(9):993-1011.
    doi: 10.1038/s41423-022-00897-8pubmed: 35962190google scholar: lookup
  16. Cvitas I, Oberhaensli S, Leeb T, Marti E. Equine keratinocytes in the pathogenesis of insect bite hypersensitivity: Just another brick in the wall?. PLoS One 2022;17(8):e0266263.
    doi: 10.1371/journal.pone.0266263pubmed: 35913947google scholar: lookup
  17. Mohsen MO, Balke I, Zinkhan S, Zeltina V, Liu X, Chang X, Krenger PS, Plattner K, Gharailoo Z, Vogt AS, Augusto G, Zwicker M, Roongta S, Rothen DA, Josi R, Costa JJD, Sobczak JM, Nonic A, Brand LA, Nuss K, Martina B, Speiser DE, Kündig T, Jennings GT, Walton SM, Vogel M, Zeltins A, Bachmann MF. A scalable and highly immunogenic virus-like particle-based vaccine against SARS-CoV-2. Allergy 2022 Jan;77(1):243-257.
    doi: 10.1111/all.15080pubmed: 34496033google scholar: lookup
  18. Marsella R. Atopic Dermatitis in Domestic Animals: What Our Current Understanding Is and How This Applies to Clinical Practice. Vet Sci 2021 Jul 2;8(7).
    doi: 10.3390/vetsci8070124pubmed: 34357916google scholar: lookup
  19. Zha L, Chang X, Zhao H, Mohsen MO, Hong L, Zhou Y, Chen H, Liu X, Zhang J, Li D, Wu K, Martina B, Wang J, Vogel M, Bachmann MF. Development of a Vaccine against SARS-CoV-2 Based on the Receptor-Binding Domain Displayed on Virus-Like Particles. Vaccines (Basel) 2021 Apr 16;9(4).
    doi: 10.3390/vaccines9040395pubmed: 33923573google scholar: lookup
  20. Pechsrichuang P, Namwongnao S, Jacquet A. Bioengineering of Virus-like Particles for the Prevention or Treatment of Allergic Diseases. Allergy Asthma Immunol Res 2021 Jan;13(1):23-41.
    doi: 10.4168/aair.2021.13.1.23pubmed: 33191675google scholar: lookup
  21. Pali-Schöll I, DeBoer DJ, Alessandri C, Seida AA, Mueller RS, Jensen-Jarolim E. Formulations for Allergen Immunotherapy in Human and Veterinary Patients: New Candidates on the Horizon. Front Immunol 2020;11:1697.
    doi: 10.3389/fimmu.2020.01697pubmed: 32849594google scholar: lookup
  22. Kumar S, Gupta S, Mohmad A, Fular A, Parthasarathi BC, Chaubey AK. Molecular tools-advances, opportunities and prospects for the control of parasites of veterinary importance. Int J Trop Insect Sci 2021;41(1):33-42.
    doi: 10.1007/s42690-020-00213-9pubmed: 32837530google scholar: lookup
  23. Jonsdottir S, Fettelschoss V, Olomski F, Talker SC, Mirkovitch J, Rhiner T, Birkmann K, Thoms F, Wagner B, Bachmann MF, Kündig TM, Marti E, Fettelschoss-Gabriel A. Safety Profile of a Virus-Like Particle-Based Vaccine Targeting Self-Protein Interleukin-5 in Horses. Vaccines (Basel) 2020 May 9;8(2).
    doi: 10.3390/vaccines8020213pubmed: 32397549google scholar: lookup
  24. Foerster J, Molęda A. Virus-Like Particle-Mediated Vaccination against Interleukin-13 May Harbour General Anti-Allergic Potential beyond Atopic Dermatitis. Viruses 2020 Apr 13;12(4).
    doi: 10.3390/v12040438pubmed: 32294982google scholar: lookup
  25. Wang B, Chen S, Zheng Q, Liu Y, Shi G. Peptide-Based Vaccination Therapy for Rheumatic Diseases. J Immunol Res 2020;2020:8060375.
    doi: 10.1155/2020/8060375pubmed: 32258176google scholar: lookup
  26. Chariou PL, Ortega-Rivera OA, Steinmetz NF. Nanocarriers for the Delivery of Medical, Veterinary, and Agricultural Active Ingredients. ACS Nano 2020 Mar 24;14(3):2678-2701.
    doi: 10.1021/acsnano.0c00173pubmed: 32125825google scholar: lookup
  27. Balke I, Zeltins A. Recent Advances in the Use of Plant Virus-Like Particles as Vaccines. Viruses 2020 Feb 28;12(3).
    doi: 10.3390/v12030270pubmed: 32121192google scholar: lookup
  28. Olomski F, Fettelschoss V, Jonsdottir S, Birkmann K, Thoms F, Marti E, Bachmann MF, Kündig TM, Fettelschoss-Gabriel A. Interleukin 31 in insect bite hypersensitivity-Alleviating clinical symptoms by active vaccination against itch. Allergy 2020 Apr;75(4):862-871.
    doi: 10.1111/all.14145pubmed: 31816097google scholar: lookup
  29. Kratzer B, Hofer S, Zabel M, Pickl WF. All the small things: How virus-like particles and liposomes modulate allergic immune responses. Eur J Immunol 2020 Jan;50(1):17-32.
    doi: 10.1002/eji.201847810pubmed: 31799700google scholar: lookup
  30. Henrique MO, Neto LS, Assis JB, Barros MS, Capurro ML, Lepique AP, Fonseca DM, Sá-Nunes A. Evaluation of inflammatory skin infiltrate following Aedes aegypti bites in sensitized and non-sensitized mice reveals saliva-dependent and immune-dependent phenotypes. Immunology 2019 Sep;158(1):47-59.
    doi: 10.1111/imm.13096pubmed: 31315156google scholar: lookup
  31. Mohsen MO, Heath MD, Cabral-Miranda G, Lipp C, Zeltins A, Sande M, Stein JV, Riether C, Roesti E, Zha L, Engeroff P, El-Turabi A, Kundig TM, Vogel M, Skinner MA, Speiser DE, Knuth A, Kramer MF, Bachmann MF. Vaccination with nanoparticles combined with micro-adjuvants protects against cancer. J Immunother Cancer 2019 Apr 26;7(1):114.
    doi: 10.1186/s40425-019-0587-zpubmed: 31027511google scholar: lookup
  32. von Loga IS, El-Turabi A, Jostins L, Miotla-Zarebska J, Mackay-Alderson J, Zeltins A, Parisi I, Bachmann MF, Vincent TL. Active immunisation targeting nerve growth factor attenuates chronic pain behaviour in murine osteoarthritis. Ann Rheum Dis 2019 May;78(5):672-675.
    doi: 10.1136/annrheumdis-2018-214489pubmed: 30862648google scholar: lookup
  33. Bachmann MF, El-Turabi A, Fettelschoss-Gabriel A, Vogel M. The Prospects of an Active Vaccine Against Asthma Targeting IL-5. Front Microbiol 2018;9:2522.
    doi: 10.3389/fmicb.2018.02522pubmed: 30405579google scholar: lookup
  34. Fettelschoss-Gabriel A, Fettelschoss V, Olomski F, Birkmann K, Thoms F, Bühler M, Kummer M, Zeltins A, Kündig TM, Bachmann MF. Active vaccination against interleukin-5 as long-term treatment for insect-bite hypersensitivity in horses. Allergy 2019 Mar;74(3):572-582.
    doi: 10.1111/all.13659pubmed: 30402930google scholar: lookup
  35. Anzaghe M, Schülke S, Scheurer S. Virus-Like Particles as Carrier Systems to Enhance Immunomodulation in Allergen Immunotherapy. Curr Allergy Asthma Rep 2018 Oct 25;18(12):71.
    doi: 10.1007/s11882-018-0827-1pubmed: 30362017google scholar: lookup
Subscribe to our newsletter
Join 99,928 horse owners like you who receive our email updates on horse health and nutrition.