Treating insect-bite hypersensitivity in horses with active vaccination against IL-5
<p><strong>Background</strong> 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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Elsevier
2018
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| _version_ | 1797076219212070912 |
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| author | 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, T Bachmann, M |
| author_facet | 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, T Bachmann, M |
| author_sort | Fettelschoss-Gabriel, A |
| collection | OXFORD |
| description | <p><strong>Background</strong> 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.</p> <p><strong>Objective</strong> To target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils.</p> <p><strong>Methods</strong> 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).</p> <p><strong>Results</strong> 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.</p> <p><strong>Conclusion</strong> 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.</p> |
| first_indexed | 2024-03-07T00:01:02Z |
| format | Journal article |
| id | oxford-uuid:75f53a39-f1ad-4854-891f-1db24a9f6674 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:01:02Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | oxford-uuid:75f53a39-f1ad-4854-891f-1db24a9f66742022-03-26T20:12:39ZTreating insect-bite hypersensitivity in horses with active vaccination against IL-5Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:75f53a39-f1ad-4854-891f-1db24a9f6674EnglishSymplectic Elements at OxfordElsevier2018Fettelschoss-Gabriel, AFettelschoss, VThoms, FGiese, CDaniel, MOlomski, FKamarachev, JBirkmann, KBühler, MKummer, MZeltins, AMarti, EKündig, TBachmann, M<p><strong>Background</strong> 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.</p> <p><strong>Objective</strong> To target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils.</p> <p><strong>Methods</strong> 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).</p> <p><strong>Results</strong> 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.</p> <p><strong>Conclusion</strong> 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.</p> |
| spellingShingle | 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, T Bachmann, M Treating insect-bite hypersensitivity in horses with active vaccination against IL-5 |
| title | Treating insect-bite hypersensitivity in horses with active vaccination against IL-5 |
| title_full | Treating insect-bite hypersensitivity in horses with active vaccination against IL-5 |
| title_fullStr | Treating insect-bite hypersensitivity in horses with active vaccination against IL-5 |
| title_full_unstemmed | Treating insect-bite hypersensitivity in horses with active vaccination against IL-5 |
| title_short | Treating insect-bite hypersensitivity in horses with active vaccination against IL-5 |
| title_sort | treating insect bite hypersensitivity in horses with active vaccination against il 5 |
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