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

J Allergy Clin Immunol. 2018 Oct;142(4):1194-1205.e3. doi: 10.1016/j.jaci.2018.01.041. Epub 2018 Apr 4.

Abstract

Background: 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.

Objective: To target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils.

Methods: 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).

Results: 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.

Conclusion: 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.

Keywords: Allergic dermatitis; eosinophils; vaccination.

Publication types

  • Clinical Trial, Veterinary
  • Research Support, Non-U.S. Gov't

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*

Substances

  • Autoantibodies
  • Interleukin-5
  • Immunoglobulin E