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 ( IBH ) in horses is a chronic allergic dermatitis caused by insect bites. Horses suffer from pruritic skin lesions, caused by type‐I/type‐ IV allergic reactions accompanied by prominent eosinophil infiltration into the skin. Interleukin‐5 ( IL ‐5) is the key cytokine for eosinophils and we have previously shown that targeting IL ‐5 by vaccination reduces disease symptoms in horses. Objective Here, we analyzed the potential for long‐term therapy by assessing a second follow‐up year of the previously published study. Methods The vaccine consisted of equine IL ‐5 ( eIL ‐5) covalently linked to a cucumber mosaic virus‐like particle ( VLP ) containing a universal T cell epitope (Cu MV TT ) using a semi‐crossover design to follow vaccinated horses during a second treatment season. Thirty Icelandic horses were immunized with 300 μg of eIL ‐5‐Cu MV TT without adjuvant. Results The vaccine was well tolerated and did not reveal any safety concerns throughout the study. Upon vaccination, all horses developed reversible anti‐ eIL ‐5 auto‐antibody titers. The mean course of eosinophil levels was reduced compared to placebo treatment leading to significant reduction of clinical lesion scores. Horses in their second vaccination year showed a more pronounced improvement of disease symptoms when compared to first treatment year, most likely due to more stable antibody titers induced by a single booster injection. Hence, responses could be maintained over two seasons and the horses remained protected against disease symptoms. Conclusion Yearly vaccination against IL ‐5 may be a long‐term solution for the treatment of IBH and other eosinophil‐mediated diseases in horses and other species including humans.

Background Insect bite hypersensitivity (IBH) is the most common seasonal pruritic allergic dermatitis of horses occurring upon insect bites. In recent years, a major role for IL‐31 in allergic pruritus of humans, monkeys, dogs, and mice was acknowledged. Here, we investigate the role of IL‐31 in IBH of horses and developed a therapeutic vaccine against equine IL‐31 (eIL‐31). Methods IL‐31 levels were quantified in allergen‐stimulated peripheral blood mononuclear cells (PBMCs) and skin punch biopsies of IBH lesions and healthy skin from IBH‐affected and healthy horses. The vaccine consisted of eIL‐31 covalently coupled to a virus‐like particle (VLP) derived from cucumber mosaic virus containing a tetanus toxoid universal T‐cell epitope (CuMVTT). Eighteen IBH‐affected horses were recruited and immunized with 300 μg of eIL‐31‐CuMVTT vaccine or placebo and IBH severity score was recorded. Results IL‐31 was increased in PBMCs and exclusively detectable in skin lesions of IBH‐affected horses. Vaccination against eIL‐31 reduced delta clinical scores when compared to previous untreated IBH season of the same horses and to placebo‐treated horses in the same year. The vaccine was well tolerated without safety concerns throughout the study. Conclusion TH2‐derived IL‐31 is involved in IBH pathology and accordingly the immunotherapeutic vaccination approach targeting IL‐31 alleviated clinical scores in affected horses.