The type of allergic dermatitis known as Queensland Itch, Summer or Sweet Itch has so far proven impossible to cure and difficult to manage, but a new study suggests a vaccine may soon be available to provide the relief horses and their owners are looking for.
Insect bite hypersensitivity (IBH) is an allergic reaction to the bite of the female Culicoides midge, a blood-sucking insect found in all countries except Antarctica, New Zealand and Iceland. First described as ‘recurring Summer dermatitis’ by French researchers in 1937, IBH affects horses of all breeds, and in Queensland alone, up to 60% of horses are IBH-affected.
A research team headed by Dr Antonia Gabriel from the Department of Dermatology at the University Hospital Zurich, Switzerland, is the first to develop and successfully trial a therapeutic vaccine to treat this chronic, allergic condition. It is hoped that, as well as treat horses, it may lead to the development of a similar vaccine for humans.
Dr Gabriel says: “As well as protecting from infectious diseases, vaccines can be used in a therapeutic setting, such as in chronic or recurrent diseases. [Using vaccines] is similar to long-term treatment with monoclonal antibodies in humans, however, the latter require more frequent injections with higher doses (bodyweight-dependent), and are also much more expensive than vaccines.”
Whereas some horses tolerate the Culicoides insect bites without a problem, the immune system of IBH-affected horses overreacts when it detects the presence of several of the proteins contained in the saliva of the midge.
The reaction causes the body to secrete mediators that induce skin inflammation in order to attract more immune cells (particularly eosinophils, a type of white blood cell) to ‘fight’ the allergens and, in doing so, cause tissue damage and further exaggerate the inflammation.
Clinically, the sites of the insect bites become inflamed and very itchy, motivating the intense scratching that leads to hair loss and skin lesions.
The self-trauma contributes to secondary infections and the condition often progresses to become chronic. It leads to permanent scarring, scaling, thickening, and the formation of ridges and folds on the skin. Because the midges prefer to feed along the horses’ topline and belly, these areas are the most commonly affected.
For their studies, the researchers recruited a number of Icelandic horses living in Switzerland. During the season before vaccination, they symptom-scored the horses’ skin lesions and analysed their blood for both the eosinophil counts and Culicoides species-specific immunoglobulin E (IgE) levels, which indicate an allergic response to the Culicoides midge.
Interestingly, they found the severity of the clinical symptoms in IBH-affected horses was strongly correlated with the presence of massive amounts of inflammation-inducing eosinophils, whereas the levels of IgE were not as reliable indicators. This finding encouraged the researchers to develop a therapeutic vaccine against equine IL-5 (eIL-5), the master regulator of eosinophils, as a means to moderate the level of the body’s response.
After designing and producing the vaccine, the following season, they divided 34 horses into two groups and performed a double-blind, placebo-controlled randomised trial. Neither the persons performing the clinical trial nor their owners knew which horses received the vaccine with the eIL-5 or the placebo vaccine.
The vaccine was well tolerated and did not reveal any safety concerns, but was able to induce anti-eIL-5 autoantibody titers in 17 out of 19 horses treated with the vaccine. This resulted in a significant reduction in clinical lesion scores when compared with previous season levels, and the vaccinated horses also scored lower than the placebo-treated horses.
Clinical improvement by scoring of skin lesions showed that 47% of vaccinated horses reached 50% improvement and 21% reached 75% improvement. In the placebo group, 13% of horses showed a 50% improvement (this could be attributed to the seasonal variations) and no horse reached 75% improvement.
“We have shown the therapeutic types of vaccines efficiently induce immune responses in horses and are thus suitable for treating chronic conditions, such as allergies and, in addition, they have an affordable price,” says Dr Gabriel.
“The next step is to proceed with regulatory studies and prepare the dossiers for vaccine manufacturing, efficacy and safety in order to apply for market authorisation, which we are aiming to complete by 2021.”
This promising study is the first successful immunotherapeutic approach targeting a chronic disease in horses, and might facilitate development of a similar vaccine against IL-5 in humans.
Treating insect-bite hypersensitivity in horses with active vaccination against IL-5 by A. Fettleschoss-Gabriel, V. Fettelschoss, F. Thoms, C. Giese, M.Daniel, F. Olomski, J. Kamarachev, K.Birkmann, M. Buhler, M. Kummer, A. Zeltins, E. Marti, T.M. Kundig and M.F. Bachmann is published in PubMed. https://www.ncbi.nlm.nih.gov/pubmed/29627082