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

使用 IL-5 主动疫苗接种治疗马的昆虫叮咬过敏症

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作者: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

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.

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.

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).

Objective

To target these cells and treat disease, we developed a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils.

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.

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