Researchers' Zone:
Mouse studies offer hope for a vaccine that treats multiple allergies at once
It is very common to have multiple allergies interacting, such as pollen and various foods, but we can only treat a few of them individually. Researchers from DTU are set to change that.
Published
The chance is high that you or someone you know are familiar with the many discomforts that come with allergies, such as sneezing, burning and itching eyes and throat, and fatigue as allergy affects a staggering 40 percent of the global population.
It is also very common to react against multiple sources at the same time, such as pollen and different foods, which makes avoidance challenging to handle.
We, a research group at DTU, have just come up with a potential solution to the main drawbacks of current treatment, showing the potential of an mRNA vaccine (yes, the same technology used in the COVID-19 vaccines) against cross-allergies.
A vaccine would be able not only to cut down on treatment time, decrease side effects, potentially benefitting patience adherence to treatment, but also to treat multiple allergies at the same time.
Our results have just been published in Nature Communication. Here, we cover the current treatment standards today and give an update on our developments going on right now.
Cross-allergy causes a tough double challenge
Pollen allergies are among the most common allergic diseases, closely followed by food allergies. However, many patients do not react to just one source.
Instead, they experience what is known as cross-allergy (allergy cross-reactivity), meaning their immune system reacts to similar allergens found in different plants or foods.
In many cases, patients first develop and allergy to pollen and later begin reacting to certain fruits, vegetables, or nuts.
This phenomenon occurs because allergens from different sources share a similar shape. Since the immune system recognizes allergens based on their shape, it may mistake proteins from different plants as being the same.
As a result, exposure to any of these related allergens can trigger allergic symptoms.
For patients, this creates a difficult double burden. They are not only sensitive to the pollen in the air, causing breathing difficulties and discomfort during pollen season, they also must watch what they eat constantly to avoid triggering food allergies.
Apples and birch pollens looks the same for the immune system
This ongoing uncertainty can be stressful and significantly impact daily life. In severe cases, allergic reactions can escalate into anaphylaxis, a potentially life-threatening condition in which airway constriction and a drop in blood pressure occur. Immediate treatment is essential.
Two important groups of cross-reactive allergens illustrate how widespread this issue is in Europe.
PR-10 proteins, found for example in apples and birch pollen, are a common cause of cross-allergy in Nordic countries.
In contrast, lipid transfer proteins (LTPs), that ispresent in peach, olive pollen, and nuts, are a major driver of cross-reactive allergies in Southern and Central Europe.
Current treatment is ineffective and uncomfortable
Right now the primary advice to people with allergies is avoidance, thus staying clear of eating what you are allergic to and restraining from going out in high pollen season.
Antihistamines or corticosteroids can be used to minimize symptoms but do not cure the underlying problem.
The only long-term treatment available for allergies has been allergen-specific immunotherapy (AIT), sometimes described as controlled micro-dosing.
This is a long-straining treatment (up to five years!), with uncomfortable secondary effects that handles one allergen source at a time, where patients are exposed to small amounts of the allergen over a long period (years), until their immune system develops tolerance.
Up to 90 percent decide to abandon treatment due to a lack of efficacy or discomfort.
The most common treatment methods are injections or sublingual tablets, but patches have also shown promising results and offer a simpler, less invasive treatment method.
If patients with cross-allergy are offered AIT-treatment, they must undergo treatment for each separate allergen, as there is no way to treat cross-allergy as a whole.
Clinicians therefore recommend AIT for the main allergens causing symptoms, which does not necessarily address allergies to other related sources.
New developments to target cross-allergies
The main challenges of the current solution are the long treatment period, the adverse side effects derived from direct exposure to the allergen, and the very narrow treatment focus that doesn't target cross-allergies.
Fortunately, in the realm of allergy immunotherapy, there is a wave of exciting technological advancements on the horizon.
Research groups from China and the USA have used mRNA as a platform for experimental allergy vaccines.
Inspired by the success of COVID-19 mRNA vaccines, they propose using similar technology to protect against allergies quickly and safely, minimizing adverse effects.
At The Section for Biologics Engineering at DTU Bioengineering we investigate this new approach and are developing a new treatment that hopefully will not only cut down on treatment time and minimizes side effects, but also targets the unmet need of cross-allergies.
A less harmful treatment
We have designed a so-called ‘consensus allergen’ that represents several common allergens in fruits, pollens, nuts, and legumes (including peanuts) from a family of allergens known as lipid transfer proteins (LTP) in a single allergen.
By delivering this consensus allergen in the form of an mRNA vaccine, we aim to reduce the side effects associated with current AIT-treatment, since the body produces the protein itself in a controlled way rather than being exposed directly to natural allergen extracts.
The goal of this mRNA-consensus-vaccine is to train your immune system to stop producing harmful IgE antibodies that, together with the allergen, can trigger an allergic reaction.
Instead, the vaccine should cause your immune system to produce neutralizing and protective IgG antibodies that can recognize the allergens and neutralize these allergens thus blocking the allergic reaction.
The vaccine increases protective antibodies in allergic mice
In our newly published study, we first immunised healthy not-allergic mice with the mRNA version of our LTP consensus allergen, and they produced high levels of protective IgG antibodies.
Importantly, the vaccine did not induce the harmful IgE antibodies that normally drive allergic reactions.
After three doses with three weeks intervals, the mice showed strong IgG responses against multiple LTP allergens found in fruits, nuts, legumes, and pollens with better coverage of sources than immunisation with a single allergen.
These antibodies were not limited to a single allergen, but they recognized a broad range of related LTP proteins.
The antibodies were further tested in laboratory experiments. Here, we used cells and blood from allergic patients and from the vaccinated mice.
The induced mouse IgG antibodies were able to block allergic patient IgE binding and prevent activation of allergy effector cells. Whether this translates into protection against symptoms in humans remains to be tested in clinical trials.
Finnaly we tested the vaccine in allergic mice. The treatment was well tolerated and significantly increased allergen-specific IgG antibodies against multiple LTP allergens from different sources, demonstrating a broad and cross-reactive protective response.
While full protection against anaphylaxis was not achieved in this early model, further optimization of dose and formulation will have to be performed and tested in the allergic mouse model.
When this is achieved, the next step will be to test the treatment in a human setting by clinical trials. But in the future, we hope that this will help translate these immune responses into complete clinical protection.
