Scientists have engineered a mRNA vaccine that can treat allergic asthma by reducing the immune system’s response. This approach could one day enable the prevention of asthma rather than just managing the symptoms.
“Currently, the general treatments for asthma could only relieve symptoms but hardly prevent the deteriorative progression of the disease,” wrote the authors of the study published in Advanced Science.
To develop an effective vaccine against asthma, the scientists put a twist on the mRNA vaccines that are currently used to prevent Covid-19. While vaccines typically prevent infections by strengthening the immune response against a specific pathogen, their vaccine was designed to do the opposite — reducing the excessive response of the immune system that causes asthma symptoms.
So far, the vaccine prototype has been successful at treating allergic asthma in mice. If this approach eventually proves to be successful in humans, it could have potential to treat many other conditions that, like asthma, are caused by an overactivation of the immune system, such as autoimmune diseases or transplant rejections.
Taming the immune system
Precisely controlling the immune response to treat conditions in which the immune system is overly active has long been a challenge for the medical field. Among other drugs, antihistamines and corticosteroids are commonly used to temporarily reduce the activity of the whole immune system. However, these effects are temporary and cause side effects, such as drowsiness in the case of antihistamines, and can make infections more likely by suppressing the natural functioning of the immune system.
To circumvent these issues, researchers are now looking to an alternative approach that relies on tolerogenic vaccines, which are vaccines that make the immune system tolerate an allergen instead of react against it.
Fazhan Wang and colleagues at Zhengzhou University aimed to create a tolerogenic vaccine for asthma based on the same principles as commercial mRNA vaccines against Covid-19. These vaccines rely on nanoparticles to carry and protect the mRNA until it reaches its target. The nanoparticles are made of lipids, a type of fat molecule that causes inflammation within the body — which in typical mRNA vaccines helps strengthen the immune response.
To make their vaccine tolerogenic, the scientists modified the lipid nanoparticles to include celastrol, a compound with anti-inflammatory and immune-suppressive properties. This compound is naturally produced by a vine plant used in traditional Chinese medicine to treat inflammatory diseases such as rheumatoid arthritis and psoriasis.
When the scientists tested these vaccines in mice, they found that vaccines carrying celastrol were able to significantly reduce the immune response against the antigen and symptoms of asthma, as compared to vaccines without the compound.
“These findings highlight the potential of our [tolerogenic mRNA] vaccine as a novel strategy for asthma treatment, warranting further research,” stated the authors.
Towards a new type of vaccine for asthma
The preliminary results achieved by Wang and colleagues show potential for their vaccine design, but the authors acknowledge their study has several limitations. One of them is that they only tested the vaccine against a single allergen, which may not reflect the variety of different allergens that can trigger asthmatic symptoms.
The study revealed that the vaccine prototype worked by targeting dendritic cells, a type of immune cell responsible for identifying threats and starting immune reactions against them. These cells then engaged other immune cells in the lungs involved in reducing inflammation and immune reactions. However, the workings of the immune system are very complex, and more research will be needed to fully understand how the vaccine works.
“While our study provides a promising proof-of-concept, validation in additional animal models, including non-human primates, is essential to advance this novel tolerogenic vaccine toward clinical application in asthma prevention and treatment,” said the authors.
They believe that, if successful in clinical trials, their vaccine design could pave the way for a range of mRNA vaccines treating a wide variety of allergy conditions beyond asthma, as well as other conditions where the immune system is dysregulated.
“[The vaccine] holds promise for therapeutic interventions in diverse immune disorders, including autoimmunity, organ transplantation, chronic infections, and allergic diseases,” they concluded.
Reference: Fazhan Wang et al., A Spleen-Targeted Tolerogenic mRNA-LNPs Vaccine for the Treatment of Experimental Asthma, Advanced Science (2025). DOI: 10.1002/advs.202412543
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