A new therapeutic antibody might effectively give horses relief from the discomfort of insect bite hypersensitivity (IBH), or sweet itch, with minimal immune system side effects.

The antibody, which is still in testing phases, reduces the binding of a specific signaling molecule to immune cells that overreact during episodes of IBH, meaning caretakers could successfully calm these allergic reactions. The reversible neutralization of that molecule could allow veterinarians to pause treatment as necessary—such as when the horse needs its full immune power to fight other diseases—and limit treatment times to only the IBH season, said Nora Langreder, PhD candidate at Technische Universität Braunschweig’s Institute for Biochemistry, Biotechnology, and Bioinformation Systems, in Germany.

“We just wanted to try a different approach” to addressing IBH, Langreder said. “Our main goal is that we want to apply an antibody that’s not enhancing any immune reaction in the horse, and just see if that’s also an alternative.”

IBH in Horses: Still Hard to Treat

Insect bite hypersensitivity causes severe itching in horses that develop allergic reactions to Culicoides—aka biting midges.

Treatment with glucocorticoids can lead to significant side effects such as metabolic disorders, increased susceptibility to infections, and laminitis, she said. Antihistamines are typically not effective for treating IBH.

So, for the most part, caretakers manage IBH by keeping horses stalled and/or covered with sheets to protect them from Culicoides bites, Langreder said.

The Critical Role of Interleukin-5 in IBH

Scientists already know the proteins in the insects’ saliva glands provoke allergic reactions in horses, said Langreder. In IBH horses those proteins cause specific kinds of allergic responses that trigger the production of a signaling cell, or cytokine, in the immune system known as interleukin IL-5 that activates special immune cells called eosinophils. In IBH reactions the eosinophils overreact, which leads to inflammation, she added.

Physicians have already started successfully treating certain kinds of human asthma with antibodies against IL-5 and its receptors.

The antibody approach is an alternative to a potential anti-IL-5 vaccine, she explained. Five years ago a Swiss research team used this concept when they created an IBH vaccine based on IL-5 attached to a viruslike particle. The study horses reacted by producing antibodies against their own IL-5 cells, resulting in significantly weaker allergic reactions.

“Both approaches have advantages and disadvantages, and, at the current time, it cannot be predicted if a reversible, more short-term or a more long-term approach is better suited against IBH,” said Michael Hust, PhD, also of Technische Universität Braunschweig.

Discovering a Stable Anti- IL-5 IgG Antibody

Langreder and fellow PhD candidate at the university Dorina Schäckermann created the short-term, reversible IBH treatment based on monoclonal immunoglobulin G (IgG) antibodies, which reach significantly lower concentrations in the blood after two to three weeks. The idea, they said, was to have greater control over any potentially negative immune side effects. In other words, such a short-term treatment would give caretakers more flexibility as they continuously weigh the risks and benefits of possible immune suppression. They engineered a molecule that avoids activating immune responses.

The team selected several antibodies against IL-5 in their laboratory to develop the optimal anti-IL-5 IgG antibody, Langreder said. After multiple tests they narrowed their candidates to one stable, easily producible, and usable antibody, NOL226-2-D10, which blocks the binding of IL-5 to its receptor.

“In vitro (in the lab), the approach is working,” Schäckermann said. “It’s a stable, monoclonal antibody that’s producible. So it’s a promising candidate.”

In ongoing tests in a small group of live horses, unpublished results show the antibody is not only safe but also probably effective, she added. “We did a first study to test safety, and we’ve had no side effects or anything so far,” she told The Horse. “And now we’re planning an extended study to test the efficacy of the antibodies.

“The plan is to start in the spring, before the season starts, so IBH doesn’t happen in the first place,” Schäckermann said. “Then continue throughout the summer with as many doses necessary for each horse.”

Further studies are needed to establish dose and how long effects would last during the midge season, the researchers added.