Researchers Developing Immunotherapeutic IBH Treatment

Veterinarians might soon have a new, high-tech "tool" to help treat seasonal equine dermatitis caused by insect bites: clones.

By cloning certain proteins found in insects, scientists hope to collect abundant and easily accessible quantities of allergens that could help produce a cure through immunotherapy, said Huub Savelkoul, PhD, professor in the cell biology and immunology group at Wageningen University in The Netherlands. The process has already helped them develop accurate diagnostic testing for the itchy allergic reaction scientists call insect bite hypersensitivity, or IBH.

IBH generally is not life threatening but can be very uncomfortable for horses due to severe itching, Savelkoul explained. “Currently there is no curative treatment available for IBH, while the need for a treatment is high,” he said. The only existing treatments for IBH are prevention (such as insect sprays, insect sheets, and stabling during peak insect hours) and topical steroid or antihistaminic creams, which don’t always appear to be helpful, Savelkoul said.

“The welfare of affected horses is seriously reduced, and the owners of such horses encounter increased costs due to attempts to control the itch, while the commercial value of the horses is reduced," Savelkoul said. "Severely affected horses sometimes even have to be euthanized.”

On the cutting edge of research for IBH treatment is immunotherapy, which works by treating horses with medicine based on the insects the horses are allergic to. It’s not the insect itself, or even the bite, that itches. It’s the allergen—a protein manufactured in the insect’s body—that causes the horses to have an itchy allergic reaction.

“Allergen-specific immunotherapy is the only causative treatment of allergy at the moment,” Savelkoul said. “It’s based on the repeated administration of the disease-eliciting allergens until the sensitivity to the administered allergens is reduced, as a result of various immunological mechanisms.”

Scientists have narrowed down the allergy-causing protein in certain midges, and they’ve already successfully treated horses using immunotherapy from allergens in the Culicoides variipennis biting midge. But because it requires about 10,000 midges to get enough proteins to treat a single horse—and it’s very hard to raise these kinds of midges in a laboratory—the treatment option isn’t very practical.

Savelkoul’s team took another insect, the Culicoides obsoletus biting midge (which is prevalent in Europe) and determined its transcriptome (a sort of “recipe book” that shows how the midge’s genes produce its proteins). Savelkoul’s team identified at least seven allergenic proteins in this midge and noted how they were produced. His team then cloned the proteins by programming laboratory Escherichia coli bacteria to produce them.

The cloned allergens produced by E. coli bacteria proved to be just as irritating to horses’ skin as the original allergens produced in the midges, Savelkoul said. In fact, they were so similar to the originals that they were used to create the first reliable blood testing system for diagnosing IBH in northwestern Europe.

“Our approach is certainly feasible all over the planet,” he said. “I am fully convinced these recombinant allergens will set the stage for the development of immunotherapy protocols, and we are already busy working on those.” Marianne Sloet van Oldruitenborgh-Oosterbaan, DVM, PhD, Dipl. ECEIM, Specialist KNMvD Equine Internal Medicine, professor in Equine Internal Medicine, of the Veterinary Faculty at Utrecht University; Edwin Tijhaar, PhD, assistant professor; and Nathalie van der Meide, PhD candidate, collaborated on the study.

The study, "Cloning and expression of candidate allergens from Culicoides obsoletus for diagnosis of insect bite hypersensitivity in horses," will appear in an upcoming issue of Veterinary Immunology and Immunopathology

Disclaimer: Seek the advice of a qualified veterinarian before proceeding with any diagnosis, treatment, or therapy.