A double blow to asthma
Biologists have tested a new remedy for chronic allergic asthma
Maria Azarova, Naked Science
Asthma is the most common chronic lung disease, including among children: according to WHO, it affects about 250-300 million people worldwide and at least 250 thousand die annually. About 20% of patients face an uncontrolled course of moderate to severe disease, manifested by persistent symptoms, decreased lung function and recurrent exacerbations, despite taking medications. Heterogeneity of asthma phenotypes remains a problem for adequate assessment and treatment. However, it is known that the second type of inflammation, characterized by the production of hormone-like proteins called interleukin-4 (IL-4) and interleukin-13 (IL-13) in the lungs, respiratory tract eosinophilia and high levels of IgE antibodies (immunoglobulins E), occurs in about half of patients.
French biologists from the Pasteur Institute in Paris have created paired vaccines that target each of these cytokines. They allow the body to produce a polyclonal antibody response by combining the target molecule with a carrier protein, which makes it immunogenic. Previously, similar vaccines were used against interferon alpha (IFNa) for the treatment of lupus.
However, the authors of the study published in the journal Nature Communications (Conde et al., Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice) were not the first to take up interleukin-4 and interleukin-13: a couple of years ago, the European Union approved a recombinant, fully human monoclonal antibody called dupixent (dupilumab) for additional therapy of moderate and severe asthma. However, treatment involves expensive injections that will have to be done for a lifetime, so a vaccine with a longer duration of action would be more cost-effective.
Laurent Reber's team first vaccinated mice suffering from chronic asthma. After the procedure, rodents showed significantly increased lung elasticity and resistance compared to the control group of animals. The effect persisted even when using the vaccines separately, but it was greatest with double vaccination.
Immunized mice also showed a 21-fold decrease in the level of immune cells, called eosinophils, in the lungs compared to rodents who received regular saline. Further analysis showed that the level of IgE antibodies, which play an important role in allergic asthma, also decreased during vaccination, as did mast cells (tissue cells of the myeloid series containing basophilic granules with histamine and heparin in the cytoplasm), which pump immunoglobulins E into the lungs.
The results are yet to be confirmed in human clinical trials, but scientists have already tested their double vaccination method on rodents expressing human IL-4 and IL-13. Although the mouse and human versions of these proteins are only 50% similar, the effects on mast cells and IgE were reproduced and preserved throughout the 11 weeks of the experiment in humanized animals.
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