Antonia Fettelschoss-Gabriel1, Victoria Fettelschoss2, Franziska Thoms3, Christoph Giese4, Michelle Daniel3, Florian Olomski3, Jivko Kamarachev5, Katharina Birkmann6, Maya Bühler6, Martin Kummer6, Andris Zeltins7, Eliane Marti8, Thomas M Kündig5, Martin F Bachmann9. 1. Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland; Evax AG, Münchwilen, Switzerland. Electronic address: Antonia.gabriel@usz.ch. 2. Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland; Evax AG, Münchwilen, Switzerland. 3. Department of Dermatology, University Hospital Zurich, Schlieren, Switzerland. 4. ETH Zurich, Institute of Molecular Biology & Biophysics, Zurich, Switzerland. 5. Department of Dermatology, University Hospital Zurich, Zurich, Switzerland. 6. Thurlandpraxis, Niederuzwil, Switzerland. 7. Latvian Biomedical Research & Study Centre, Riga, Latvia. 8. Department for Clinical Research VPH, Vetsuisse Faculty of the University of Bern, Clinical Immunology Group, Bern, Switzerland. 9. 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.
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.
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 equineIL-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.
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Authors: Antonia Fettelschoss-Gabriel; Victoria Fettelschoss; Florian Olomski; Katharina Birkmann; Franziska Thoms; Maya Bühler; Martin Kummer; Andris Zeltins; Thomas M Kündig; Martin F Bachmann Journal: Allergy Date: 2018-11-25 Impact factor: 13.146