On the trail of a vaccine against allergic asthma

Asthma is a chronicle disease affecting approximately 340 millions of people worldwide. Allergic asthma accounts for 50 % of asthma in the adult population. A new vaccine against this specific form could be developed in the upcoming years.

In May 2021, the Pasteur Institute, in association with Inserm and the French start-up company NEOVACS published a study on a vaccine project against allergic asthma tested on mice. Their aim would be to induce a long-term immune response against the elements of the body that cause this type of allergy.

Being asthmatic

Asthma is an inflammation of the bronchial tubes of the lungs causing respiratory attacks that last from a few minutes to several hours. The frequency of these attacks varies from person to person. People with asthma develop wheezing, a dry cough a feeling of tightness in the chest and have difficulty breathing. It appears due to a genetic predisposition (family history) and because of favourable factors such as smoking, pollen, dust mites, animal hair, physical effort, chemical products, air pollution or similar.

The air passes through the bronchial tubes. In a person with asthma, the walls of the bronchial tubes are thicker and very sensitive. The favourable factors mentioned previously lead to an inflammation of the bronchial tubes Which causes dilation of the mucous membrane and contraction of muscles , excreting mucus which makes the air passes more difficult. When a person has an asthma attack, they can inhale a bronchodilator, a molecule that forces the muscles of the bronchial tubes to relax so that the air can flow again. Sometimes, people with asthma are forced to take heavier treatment in form of corticosteroids, in order to make the attack subside. But even this is not always effective against severe forms.

Diagram of the onset of an asthma attack

Allergic asthma: triggers and consequences

Allergens present in the atmosphere such as dust mites, animal hair, and others will trigger an allergic reaction in the body. In asthmatics, this allergic reaction can lead to an asthma attack: this is called allergic asthma (see the article "Help me doctor, I'm allergic!"). In order to defend themselves against these foreign elements, the immune cells secrete particular antibodiescalled IgE. These antibodies bind to the allergens and allow the recruitment of immune soldiers specific to their elimination (see the article "The mechanisms of allergy"). In the event of an allergy, the body produces more antibodies than necessary, which creates significant inflammation.

Hope with the vaccine

Vaccination allows, through an injection of a chemical entity, to protect an entire population against a given disease (see the article "Vaccination: the bodyguard"). In the case of allergic asthma, it is mainly a matter of protecting the person against their own immune defenses, which tends to become inflamed too quickly.

The study conducted at the Pasteur Institute on a possible vaccine aims to reduce the production of IgE antibodies through the interleukins IL-4 and IL-13. The latter are molecules that contribute to the production of IgE antibodies. The aim of this vaccine is to make the body produce antibodies directed against these interleukins. Treatments targeting IgE already exist, but they must be taken throughout the patient's life. This vaccine aims to provide long-term immunity.

In this study, researchers developed a conjugate vaccine. A vaccine is composed of an antigen (a small molecule on the surface of the pathogen) against which we want the body to develop its immunity. A conjugate vaccine is composed of two different antigens, one strong and one weak. The weak antigen produces little or no immune response, while the strong antigen induces a very strong immune response. The two are combined in the same vaccine so that the body triggers an immune reaction against the strong antigen, and by cascade this immune reaction will react against the weak antigen.

It can be thought of as a car warning light. When a warning light comes on in the car, it is taken to the garage to fix the problem. It is not uncommon for the mechanic to find other problems to fix as well. In our case, the strong antigen is the CRM197 protein, a non-toxic mutant (modified by researchers) of the diphtheria toxin, and it is our car light that makes us take it to the garage. The immune system will be activated by this unknown protein used in many other conjugate vaccines. The weak antigens are the recombinant interleukins IL-4 and IL-13. These have structures very similar to IL-4 and IL-13 in the body but cannot induce IgE production. These are the little things about the car that you wouldn't have known about if you hadn't taken it to the mechanic.

Diagram of how a conjugate vaccine works

This conjugate vaccine was tested in mice. The results showed that 6 weeks after the first injection, 90% of the mice had a high level of antibodies to IL-4 and IL-13, strong enough to neutralize interleukin activity and prevent IgE production. After one year, 60% of these mice retained antibody levels. The researchers also found that the vaccine reduced asthma symptoms and had no side effects.

Representation of the level of antibodies against interleukins IL-4 and IL-13 in mice 6 weeks and 12 months after vaccine injection

These results are very promising and suggest that with a second dose of this vaccine, the antibody level would increase again. Clinical trials, supervised tests of this vaccine on volunteers, whether or not ill, are now needed to determine the doses to be administered, the potential side effects and the number of injections required for optimal immunity. The vaccine is a real hope for all people with allergic asthma, especially in its severe form.