Αρχειοθήκη ιστολογίου

Πέμπτη 5 Απριλίου 2018

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

Publication date: Available online 4 April 2018
Source:Journal of Allergy and Clinical Immunology
Author(s): Antonia Fettelschoss-Gabriel, Victoria Fettelschoss, Franziska Thoms, Christoph Giese, Michelle Daniel, Florian Olomski, Jivko Kamarachev, Katharina Birkmann, Maya Bühler, Martin Kummer, Andris Zeltins, Eliane Marti, Thomas M. Kündig, Martin F. Bachmann
BackgroundInsect-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.ObjectiveTo target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils.MethodsThe 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).ResultsThe 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.ConclusionOur 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.

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