Researchers at the University of Zaragoza have successfully used a live attenuated vaccine against tuberculosis to reverse the role of asthma in animal models. In the future, they may become an alternative method of treating diseases that affect more than 300 million people worldwide.
of Live attenuated vaccine, Called BCG (BaciloCalmette-Guérin)y MTBVAC (Mycobacterium tuberculosis vaccine), may exceed the benefits of preventing the disease.Researcher-led work Nacho Aguiló Studies by the University of Zaragoza, the Respiratory Disease Biomedical Research Network (CIBERES) and the Aragón Institute of Health (IIS-Aragón) have shown that they can reverse the role of asthma in animal models.
In particular, when these vaccines are directly administered to the lungs of mice that have previously caused allergic reactions, their positive effects have been observed.The research results have been published in the journal Electronic biomedicine A member of the Lancet Group.
This asthma It is characterized by aggravating the inflammatory response in the lungs, thereby reducing its function, and manifesting as fatigue and shortness of breath. At present, its incidence has reached the pandemic level, 300 million boxes worldwideAccording to the World Health Organization.
In recent decades, the number of cases of this disease has increased, mainly among children in developed countries. This may be due in particular to changes in lifestyle, increasing urbanization and decreasing contact with nature.
In this case, this new study suggests that BCG or MTBVAC may be a viable alternative for the treatment of asthma.The fact that they are vaccines Safety has been tested in humans And their industrialized production will bring huge advantages to their possible clinical applications. However, more research is about to be realized.
The challenges of partial lung delivery
One of the challenges is that there is currently no treatment based on lung vaccination. In this sense, as part of the European Commission’s TRANSVAC project, in cooperation with the Rhesus Biomedical Research Center (BPRC) in the Netherlands, an experiment is planned to test the management of MTBVAC in macaques through aerosol.
The non-specific effects of live tuberculosis vaccines (such as BCG or MTBVAC) have allowed them to be used to treat different tuberculosis diseases. In fact, the current BCG vaccine can reduce infant mortality and has been the first-line treatment for infant BCG for more than 40 years. Non-invasive bladder cancer.Recently, this effect has also shown MTBVAC in the mouse model.
In the past decade, decisive steps have been taken to understand the non-specific benefits of these vaccines, which seem to be based on their ability to train the innate immune system, which is called “Well-trained immunity‘.
“For the MTBVAC vaccine, our group Prove in 2020In collaboration with Mihai Netea’s team at Radboud University in the Netherlands, MTBVAC induced a trained immune response similar to BCG, and it produced non-specific protection against pneumococcal infection in mice,” Aguiló pointed out.
The members of the genetics research team also added: “Different research groups from all over the world are conducting research to try to develop these characteristics of these vaccines against different diseases such as cancer, diabetes and even covid-19.” Carlos Martin (Carlos Martín) Mycobacterium research directed by Professor.
Asthma is a very heterogeneous disease, which may be caused by a variety of factors, but it usually leads to increased inflammation at the lung level, and in many cases, abnormal infiltration of eosinophils in the lungs.
The inflammatory process leads to abnormal mucus secretion, narrowing of the bronchi and decreased lung function, which is reflected in the patient’s fatigue and shortness of breath.
Although it is a controllable disease in most cases, it worsens the quality of life in many cases, and controlling it requires long-term treatment to reduce the symptoms of the disease, not the cause. In addition, in a significant proportion of patients, the disease exhibits severity and does not respond to conventional anti-inflammatory treatments.
Direct lung immune response
The research team led by Nacho Aguiló has spent many years studying the use of alternative ways of applying the tuberculosis vaccine. In the specific case of the pulmonary pathway, this pathway has the characteristic of inducing a direct immune response in the lung, which cannot be achieved by other pathways, such as the intradermal pathway currently used clinically for BCG and MTBVAC.
In particular, these researchers found that these vaccines induced a type 1 immune response in the lungs and hypothesized that it could counteract the type 2 characteristic inflammation that occurs in asthma. As part of the researcher Raquel Tarancón’s Ph.D. work, they developed different experimental models of mouse asthma to prove this hypothesis.
The results of the article show that in these experimental models, pulmonary administration of vaccines can greatly reverse the characteristic asthmatic response, resulting in the reduction of so-called IL-4, IL-5 and IL-13 cytokines. Pulmonary eosinophils increase or eosinophil infiltration disappears, lung epithelial remodeling decreases, which is related to the thickening and proliferation of goblet cells produced by mucus.
In addition, these effects can be achieved with a single dose of the vaccine, and the protective effect will be maintained for at least 4 months after administration. The most noteworthy fact is that the researchers observed that when the vaccine was administered to mice that had previously been induced to suffer from asthma, these beneficial effects were also obtained in chronic models of the disease.
This may indicate that the vaccine not only has a preventive effect, but also has a therapeutic effect.The current BCG vaccine is based on the form of a live attenuated vaccine Mycobacterium bovis It was isolated from cattle and will be used for a century next year. It is still the only person approved to resist this disease.
After decades of research, the MTBVAC vaccine is the first and only vaccine based on human pathogens. Mycobacterium tuberculosis Enter the clinical trial. MTBVAC has shown its safety in research Swiss Adult Phase 1A ÿ Stage 1B of South African babies.
In the latter, a Phase 2A study is being conducted in adults and newborns with and without tuberculosis to select the dose and study its safety and immunogenicity among more participants.
Raquel Tarancón, Nacho Aguiló, etc. “By destroying the local immune environment, the effect of live tuberculosis vaccine on the treatment of confirmed asthma.” Electronic biomedicine, 2021.