A team of researchers has developed new methods to produce artificial copies of the antibodies in humans that cause anaphylaxis. The aim is to improve the medical treatment of people who are allergic to insect stings.

Approximately 30 per cent of the European population suffers from allergies and 3–5 per cent is allergic to insect venom. In Denmark alone, 50,000 people are at risk of severe allergic reactions if they are stung.

If aware of the allergy, they can currently be protected with an acute injection of adrenaline or treated with a standardised allergen vaccine. The problem is that the majority of people are not aware of their allergy. Furthermore, insect allergy sufferers do not react to the same allergens and, in some cases, the treatment therefore has a reduced effect or does not work at all. A limited protection at worst can be fatal.

“Vaccines for immunotherapy today are based on the natural sources such as venom from insects and can therefore contain very different amounts of allergens and even venom from different species of insects. All patients are treated the same way by using insect venom, and this sometimes is not ideal,” says Associate Professor Edzard Spillner.

Artificial antibodies can provide better drugs
The researchers are therefore working on developing artificial allergens that mimic the allergens in insect venom. Moreover, they aim at establishing antibodies that are similar to those antibodies that are present in patients with severe allergy to insect venom.

Associate Professor Spillner is an expert in the development and design of proteins for clinical use. In his laboratory at Aarhus University, he has produced a variety of artificial allergens and also the first artificial human antibodies to insect venom. In collaboration with other researchers at Aarhus University, the most interesting ones have been crystallised recently.

Using a special biological technology, he and his research group have carried out a comprehensive mapping of the antibodies in patient serum that can cause anaphylaxis, and this is an important step in the direction of more knowledge of allergy, particularly to insect venom.

“Once we can identify and isolate specific allergens, we have routine access to studying the molecular processes going on in the blood of allergy sufferers. The component resolved approach is a major break-through in insect venom allergy and can be a benchmark for individual immunotherapeutic treatment,” says Associate Professor Spillner.

The technology has the potential for improved and more extensive diagnostic practice. The researchers estimate that the majority of people who are allergic to insect venom are currently unaware of their condition, and are unprepared for any severe allergic reactions that can occur when they are stung.

Additionally, patients with specific recognition patterns could be identified as those being at higher risk for unsuccessful immunotherapy using insect venom

The mystery of allergy
The researchers are now working in the laboratory with blood samples from patients with allergies and they are mimicking the body’s immune system so to speak. At present, they are in the process of studying the interactions between artificial antibodies mimicking the human ones and their specific target structures from the insect venom.

They are also taking a close look at the release of mediators such as histamine, which drive the allergic reaction. Here the known allergenic antibody IgE is particularly in the spotlight.

“We can isolate and rebuild IgE from the patient’s blood and identify the target structure it reacts with. This way we can analyse how it behaves together with the insect venom or other allergens. The better we understand the molecular mechanisms of action, the greater our chances are of developing new concepts in allergy treatment” says Associate Professor Spillner.

The next step for the researchers is to describe precisely how the artificial antibodies bind to antigens, and this can be the key to finding out by which factors the allergic reaction is driven.

“We don’t yet completely understand the impact of the IgE antibody binding  to the allergens on the allergic response. We’re studying the individual processes at the molecular level in the laboratory, and it will be some time before we have complete insight,” says Associate Professor Spillner.

Break-through in the laboratory
The researchers hope to obtain first answers within near future. If they succeed in identifying critical molecules, they will be able to provide better protection of individual patients. This is good news for all allergy sufferers because the method for designing artificial antibodies appears to apply to a wide range of other allergies.

“We carried out several of our experiments with allergens from insect venom, but could in principle have used all kinds of allergens. We expect to generalise our results and use the method to study the mechanisms behind many other allergic reactions,” says Associate Professor Spillner.

PHOTO TOP: One single sting can have fatal consequences for the approximately 5 per cent of the population who are allergic to insect venom. Artificial antibodies can provide key information for development of improved or new drugs, and researchers at Aarhus University have crystallised some of the first in their laboratories. The photo shows Associate Professor Edzard Spillner in the lab. (Photo: Lars Kruse)