Treating insect-bite hypersensitivity in horses with active vaccination against IL-5 - 05/10/18
, Victoria Fettelschoss, MSc a, b, Franziska Thoms, PhD a, Christoph Giese, PhD c, Michelle Daniel, BSc a, Florian Olomski, MSc a, Jivko Kamarachev, MD d, Katharina Birkmann, DVM e, Maya Bühler, DVM e, Martin Kummer, DVM e, Andris Zeltins, PhD f, Eliane Marti, DVM g, Thomas M. Kündig, MD d, Martin F. Bachmann, PhD h, iAbstract |
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.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Allergic dermatitis, eosinophils, vaccination
Abbreviations used : CMV, CMVTT, eIL-5, HRP, IBH, ISI, MALDI, MS/MS, PBST, VLP
Plan
| Supported by funding of the Swiss National Science Foundation (SNF grant CRSII3_154490), Stiftung und Verein Forschung für das Pferd/Pro Pferd (grant 2014/02), the Commission for Technology and Innovation (CTI grant 25758.1 PFLS-LS), and Benchmark Vaccines Limited, UK, through a licensing agreement with Evax AG. |
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| Disclosure of potential conflict of interest: A. Fettelschoss-Gabriel reports grants from the University of Zurich and other support from University Hospital Zurich, personal fees and nonfinancial support from Evax AG, and personal fees and nonfinancial support from Evax and has a patent (PCT/EP2016/071078) pending to Benchmark Animal Health Limited. V. Fettelschoss reports personal fees from Evax AG. F. Thoms is an employee of HypoPet AG (formerly Saiba Biotech GmbH). A. Zeltins reports a grant from EVAX AG and employment from the Latvian Biomedical Research and Study Center, Riga, Latvia. T. M. Kündig reports grants from CTI, Sinergia SNF, and MERIT and personal fees from Evax AG. M. F. Bachmann reports personal fees from Evax AG and personal fees and nonfinancial support from Saiba GmbH and has a patent (PCT/EP2016/071078) pending to Benchmark Animal Health Limited. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 4
P. 1194 - octobre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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