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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:142

Article

Fettelschoss-Gabriel, Antonia^1,2  Fettelschoss, Victoria^1,2  Thoms, Franziska¹  Giese, Christoph³  Daniel, Michelle¹  Olomski, Florian¹  Kamarachev, Jivko⁴  Birkmann, Katharina⁵  Buhler, Maya⁵  Kummer, Martin⁵  Zeltins, Andris⁶  Marti, Eliane⁷  Kundig, Thomas M.⁴  Bachmann, Martin F.^8,9 

[1] Univ Hosp Zurich, Dept Dermatol, Schlieren, Switzerland

[2] Evax AG, Munchwilen, Switzerland

[3] Swiss Fed Inst Technol, Inst Mol Biol & Biophys, Zurich, Switzerland

[4] Univ Hosp Zurich, Dept Dermatol, Zurich, Switzerland

[5] Thurlandpraxis, Niederuzwil, Switzerland

[6] Latvian Biomed Res & Study Ctr, Riga, Latvia

[7] Univ Bern, Clin Immunol Grp, Vetsuisse Fac, Dept Clin Res VPH, Bern, Switzerland

[8] Univ Bern, Inselspital, RIA Immunol, Bern, Switzerland

[9] Univ Oxford, Nuffield Dept Med, Jenner Inst, Henry Wellcome Bldg Mol Physiol, Oxford, England

关键词: Allergic dermatitis;    eosinophils;    vaccination;   

DOI  :  10.1016/j.jaci.2018.01.041

来源: Elsevier

【 摘 要 】

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 mu g 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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