Allergy vaccination


The allergy gone after three vaccinations - is it possible?

At the Karolinska Institutet in Solna, feverish work is currently underway to realize the dream of many fur allergy sufferers. Finding a cure for horse, dog and cat allergies. With allergy vaccination.

The technique is called allergy vaccination or hyposensitization, and is not really new. Allergy vaccination has existed since before, but the results of the vaccination for dog allergy in particular have been poor. Associate Professor Hans Grönlund and his research group are now investing in improving both the vaccine and the injection technique. The goal is that after three to four vaccinations you should be rid of your allergy.

- I envision a life where allergy sufferers can live together with their dog and cat. And I actually think it's entirely possible. I have good hope that we will succeed, says Hans Grönlund.

Hyposensitization is a well-documented method that consists of getting the body used to the so-called allergen, the substance you are allergic to, through repeated injections. You simply expose the immune system to a successively increasing dose of the substance, and thus get used to the immune system, injection by injection.
- Traditional hyposensitization involves slowly increasing the dose of allergen by giving a vaccination once a week, for ten weeks. Then you continue with a maintenance dose for 3–5 years. In total, there can be up to 40–60 injections, says Hans Grönlund.

Home delivery to the immune factory - Good effect of allergy vaccination

But the long treatment period and the large number of injections mean that only a few allergy sufferers, around 5%, choose to undergo the treatment. Therefore, a lot of research is being done on new techniques to reduce the number of injections, and the hope for a simpler and faster immunity is increasing. Instead of injecting the vaccine under the skin or into the muscle, one can instead inject the substance directly into a lymph node, the body's own immune factory.

The technique is called intralymphatic immunotherapy and is today a relatively large research area within immunomedicine. And several studies show good effects, already after a few injections. In the scientific journal 'Journal of allergy and clinical immunology', Hans Grönlund together with a Swiss research group already published the results of a study with intralymphatic immunotherapy against cat allergy a few years ago. It was then able to show that intralymphatic injection of cat allergy vaccine gave a very good result, already after three injections.

Effective protection after just three injections

A total of 20 cat allergy sufferers participated in the study. Twelve were injected with cat allergy vaccine and 8 with placebo, after an appropriate lymph node in the patient's groin was located by ultrasound. The study was so-called double-blind, which means that both patient and healthcare staff were unaware of which solution the patient was injected with. The allergy sufferers received a total of three vaccine injections at one-month intervals.

After completion of the treatment, a series of different tests were performed to evaluate the treatment. In a so-called nasal provocation test, the patient had cat allergen sprayed into the nose, after which the airflow was measured. This is a measure of how much the nasal mucosa swells in the presence of the allergen. They also performed so-called prick tests, where the allergic reaction is measured after injecting cat allergen under the skin, as well as various measurements of the body's immune response.

It could then be seen that patients who received the cat vaccine showed an average 74-fold improvement in the nasal provocation test, while the results of the placebo patients only increased marginally. A significant improvement could also be seen in the dot test. The immune system was highly activated in the vaccine group. Among other things, one could see that the number of 'good antibodies' (IgG) increased, while no such change could be detected in the placebo group. The results of the three injections in the groin were roughly equivalent to the average results shown with the traditional allergy vaccination, but now with only three shots.

Disinterested industry

Despite the promising results the cat study showed, they did not manage to get the product out to patients that time. They searched, but found no funding for the costly step from laboratory to patient. The major pharmaceutical companies proved uninterested in a vaccine that cures cat allergies by offering an effective allergy vaccination, and the project was dropped.
- I myself spoke to a representative from a large international pharmaceutical company, says Hans. He explained to me that 'We make in the order of a hundred billion in pure profit on anti-allergy medicine. Developing a cure would therefore be financially unwise'. The pharmaceutical industry is simply not interested in preparations like this, says Hans.

But Hans does not give up at first. Now he knows that a vaccine against fur animals could work. He knows the techniques, and they might as well be applied to a dog vaccine. But he is not satisfied with that, but is now aiming for a combined vaccine against both horses, dogs and cats. And there is a good thought behind it, as many fur allergy sufferers are hypersensitive to not just one, but several fur allergens. In other words, an allergy vaccination that works against both horses, dogs and cats.

Because although the cat vaccination study was limited, only 20 patients participated, the results were promising. The study can be considered a first step towards intralymphatic immunotherapy with other fur allergens. And including the dog's. Because the dog allergy vaccine that is on the market today has been shown to work very poorly. But it mainly does not depend on where the vaccine is injected, says Hans.

Allergist with dog sneezes before she received allergy vaccination Allergies in children and young people are on the rise. Almost every fifth child is allergic to pollen or fur animals, and more and more families are denied the opportunity to have a dog.

Random mix

- The bad effect of the dog vaccine is simply due to the fact that the vaccine does not contain all the allergens that the dog secretes. The concentration of the allergen is also not standardized, which together means that you can get insufficient doses of certain allergens in your syringe, and then you will not be fully immunized, says Hans Grönlund.

The allergy vaccination used today contains natural extracts from dogs. You simply extract the allergen from the dog's fur by washing it, and then purify the substances that cause allergies, says Hans Grönlund. But different dogs excrete different amounts and different concentrations of the six different allergens. It has been seen that the variation is great between individuals, much greater than between races. And that means that chance actually determines what the allergen mix you get by cleaning the dog's fur looks like. It simply depends on which dog you use.

When you now aim to make a combined cat, dog and horse allergy vaccine, you therefore invest in both a more effective and faster treatment method through intralymphatic injection, but also to improve the components of the vaccine itself. With the help of biotechnological methods, they want to standardize the allergen, gain control over each vaccine dose and significantly improve the results of dog allergy vaccination.

Hans explains that today we know exactly what the dog's, horse's and cat's most important allergen looks like. They can therefore be manufactured artificially in the laboratory, and thus have full control over the contents of the vaccine dose. You have bacteria to help you.
- Today, you can order the gene for the allergen or protein you are interested in, says Hans. By introducing it into a certain type of bacteria, you make it start producing the allergen. And after cleaning away all the proteins that the bacterium normally produces, you only have the active substance left.

Bo Karlstedt (left) and Hans Grönlund (th) work side by side towards a major common goal; to eradicate fur allergy. Now they are launching a test that enables the matching of dog and human, an opportunity to find a more "allergy-friendly dog" for you who suffer from allergies. - We should not have allergies in our society, says Hans Grönlund, researcher at Karolinska Institutet. His research group has developed a vaccine against dog allergy, which is believed to have gone through all clinical trials within 5-6 years. The goal is for the patient to be completely free of his fur allergy.

Pre-built molecule

Hans shows the laboratory, and the bacteria. They live on small round plates in warming cabinets. And in exchange for nutrition and heat, they manufacture various allergens, which are then extracted and assembled into a single large vaccine molecule.
- Some build houses, we build vaccine molecules, says Hans. And now it is ready. We have succeeded in building a molecule where all the allergens are now lined up, like pearls in a necklace.

A special protein sequence has also been mounted on the molecule to reduce the risk of side effects, an otherwise relatively common problem with allergy vaccination. The protein ensures that the molecule cannot circulate freely in the body, but is quickly taken up by the nearest immune cell. This, Hans explains, greatly reduces the risk of side effects. A different protein sequence makes the vaccine molecule more visible to the immune cells, which should increase its effectiveness.
- Assembling such protein sequences on natural extracts does not work, explains Hans. It can only be done with biotechnological methods. And that is another reason why it is so important to be able to produce the allergen artificially, in the laboratory, and not via washing a dog's fur.

The last, most important step

After many years of studies and trials, Han's research group has now succeeded in putting together a combined fur allergy vaccine. The molecule is ready and its safety and efficacy have been tested in several mouse experiments. But mice are not people, and much work still remains.
- Now we are taking on the big challenge of getting the vaccine to patients. Before that can happen, the product must undergo strict trials in various phases. And it is time-consuming and above all costly work, says Hans Grönlund.

But this time they don't want to take any risks. The product must go out to the patient. Hans Grönlund therefore founded, together with author and cat allergist Liza Marklund, the company Medi-Tec, which is behind the research. With a company behind them, they hope to be more successful with the financing, and right now they are looking for money to eventually be able to investigate the effect and effectiveness of the vaccine in patients.

In the meantime, Medi-Tec wants to do everything it can to help allergy sufferers and dogs live side by side. That's why the Allergenius® Dog allergen test is now being launched, a test where you can find out how allergic your dog is. In combination with this, you as an allergist can also find out which of the dog's six allergens you are allergic to, in order to have the opportunity to get a dog that fits your own allergy profile. In addition to this, Medi-Tec also works to develop allergen suppressing products to make dogs more allergy-friendly, and has just launched a special shampoo that effectively washes away allergens, as well as moisturizes and cares for the dog's skin. Even this product can be of great use, the researchers believe.

But what will hopefully be the final solution to the allergy problem, what all dog-loving fur allergy sufferers dream of - the vaccine, has gone through the clinical trials in 5-6 years, it is believed. Then, if everything went as it should, it can come out to the patient. And if it does, is it worth waiting for this allergy vaccination?

Fact box:

Fact allergy

> About 15% of Sweden's population, i.e. over 1 million people, are allergic to fur animals.

> the substance that the allergy sufferer's immune system reacts against is called an allergen and is actually a completely normal protein with an important function in the body of the dog, cat or horse.

> In cats, there is a main allergen, called Fel-d1. Over 90% of cat allergy sufferers are sensitive to this particular allergen.

> In horses, the allergen is not as well researched. Four allergens are known, but there are probably more.

> Six different allergens have been identified in dogs. they are secreted in the dog's saliva and in skin flakes. one of them, called Can f-5, is found only in the urine of unneutered male dogs.

> Research has shown that different dogs excrete different amounts of the six allergens, i.e. dogs have a highly personal allergen profile. the same applies to allergy sufferers. You can therefore be sensitive to certain dog allergens (and therefore certain dogs), but completely tolerate others.

> At the Karolinska Institutet, research is being conducted to cure, or at least greatly suppress fur allergy with only 3-4 vaccinations.

> While the vaccine is going through clinical trials, there is now a test to analyze the dog's allergen profile. The researchers have also developed shampoo products to make the dog's fur less allergenic.

This is the second part in a mini-series about the research at KI. Part 1 can be read in HSS no. 1/2015, you will find it here .

Text and photo: Katarina Sundberg. The article was published in Hundsport Special no. 2/2015.