Pr Laurent Guilleminault: “Vaccination can make a patient produce therapeutic antibodies”

Today: Is the acute asthma vaccine no longer science fiction?

PROF. GILEMENO: At least it’s under study. This is possible today, because the pathophysiology of severe asthma is better known, in particular the involvement of cytokines, which play a major role in inflammation, such as interleukin-4, 5 and 13. We already have therapeutic antibodies directed against interleukin-5, or against the interleukin-4 receptor ( Common to interleukin 13). These therapeutic monoclonal antibodies give very good results, but their production is very expensive. To overcome this particular production problem, our research team (located at the Institut Infiniti in Toulouse) is working in collaboration with Neovacs to develop a vaccine, which will be able to produce these antibodies to the same organism. These antibodies naturally fight inflammatory cytokines.

How do we wish to produce antibodies useful in severe asthma with a vaccine?

To produce the vaccine developed by Neovacs, a vector protein that causes an immune reaction was used, to which interleukin-4 and interleukin-13 have been linked. Objective: To stimulate the production of antibodies directed against IL-4 and IL-13 and thus lead to the inhibition of these cytokines and, in fact, to have a beneficial effect on asthma. It should be noted that IL-4 and IL-13 are also implicated in other allergic diseases, such as atopic dermatitis or food allergy, hence this association was selected.

When do we expect this vaccine to appear on the market?

For now, we’re still in the research phase, with preclinical studies in animals. The first results showed a beneficial effect in cases of severe asthma, both preventive and curative, which is encouraging. Development must now continue with clinical studies in the coming years: if all goes well, commercialization may be possible in the next five to ten years.

What about monoclonal antibodies marketed in severe asthma?

Four are marketed. These drugs are mepolizumab (anti-IL-5), benralizumab (anti-IL-5), dupilumab (anti-IL-4), and omalizumab (anti-IgE). These antibodies are used in patients with severe asthma who have exacerbations that require (healthy) oral cortisone treatments.

This year, the great new was the publication of the Navigator study, which shows the effectiveness of tézepelumab, a new therapeutic antibody with a different target. In fact, TSLP targets (Thymic stromal lymphopoietin), which are directly secreted by the respiratory epithelium, which makes it possible to further interfere with the beginning of the inflammatory cascade. This new treatment, which has been shown to be effective in patients with severe asthma, is available at the ATU and pending MA.

Whereas with other antibodies some biomarkers are required (eosinophils, regulatory T lymphocytes, etc.), tézepelumab appears to be effective regardless of the biomarkers of our patients, and therefore can be directed to all patients with severe asthma.

Are other molecules under development?

Therapeutic antibodies with a long half-life are already in development and could reach the market in the not too distant future. They will be given twice a year – instead of subcutaneously every 2, 4 or 8 weeks as is currently the case, thus greater convenience for our patients. The first data, which is still very preliminary, were presented at the European Congress of Pulmonology.

What about the last patients still getting away with all these treatments?

Some of them may have been classified as asthmatic, when in fact they are not. Hyperventilation syndrome or vocal cord dyskinesia are differential diagnoses that are sometimes confusing, but if a patient misclassified as asthmatic receives treatment for asthma, there is no escaping it.

But the main cause of failure remains associated with asthma patients who do not comply with their treatment, even if they claim otherwise. Due to non-compliance or inadequate inhaled therapy, 800 to 900 patients still die of asthma in France (data obtained with reference to death certificates). This illustrates the importance of disease-modifying therapies that should not be forgotten, even if there is a lot of news about innovative treatments.

Is the impact of COVID in asthmatic patients specifically related to these untreated or inadequately treated patients?

Yes, a possible association with severe forms of Covid was found only in patients with unbalanced asthma (inadequate or non-compliant treatment), recourse to repeated courses of corticosteroids, or even in the case of comorbidity (obesity in particular). Biological treatments are not associated with a serious increased risk of contracting Covid. Likewise, the vaccine against Covid protects them from dangerous forms and gestures of barrier, from the dangers of contamination (including other respiratory viruses).

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