A Potential Vaccine for Allergic Asthma
According to the Centers for Disease Control and Prevention (CDC), approximately 8% of adults and 7% of children suffer from some form of asthma in the United States. Asthma is the most common disease affecting the lungs and shows higher prevalence among low-income populations. Symptoms of asthma include wheezing, coughing, and difficulty breathing caused by inflammation, or swelling, of the airways as well as the buildup of excessive mucus. Treatments typically involve prescribed inhalers, which can administer a variety of drugs—such as corticosteroids that reduce inflammation—to combat symptoms.
However, up to 70% of people with asthma are diagnosed with severe asthma. Also known as type 2 asthma, severe asthma is difficult to treat with high-dosage inhaler medication and often requires oral corticosteroids to control it. Type 2 inflammation, an innate immune response usually seen with allergic reactions, characterizes severe asthma. People with asthma and type 2 inflammation experience asthma exacerbation when exposed to allergens such as dust mites. The underlying cause of the allergic reaction in the lungs is the activation of specialized white blood cells, the body’s main immune defense system. These blood cells release certain types of cytokines, which trigger inflammation and signal for other cells to come to the area. Interleukin-4 (IL-4) and interleukin-13 (IL-13) are two such cytokines most prevalent in type 2 asthma. Currently, researchers are conducting clinical trials involving antibody injections that target the receptors of IL-4 and IL-13 simultaneously, and preliminary results indicate that blocked interleukin signaling effectively reduces severe allergic reactions and improves lung function. However, such treatments require repeated injections over a person’s lifetime. Therefore, improvements in alternative treatments are needed.
However, up to 70% of people with asthma are diagnosed with severe asthma. Also known as type 2 asthma, severe asthma is difficult to treat with high-dosage inhaler medication and often requires oral corticosteroids to control it. Type 2 inflammation, an innate immune response usually seen with allergic reactions, characterizes severe asthma. People with asthma and type 2 inflammation experience asthma exacerbation when exposed to allergens such as dust mites. The underlying cause of the allergic reaction in the lungs is the activation of specialized white blood cells, the body’s main immune defense system. These blood cells release certain types of cytokines, which trigger inflammation and signal for other cells to come to the area. Interleukin-4 (IL-4) and interleukin-13 (IL-13) are two such cytokines most prevalent in type 2 asthma. Currently, researchers are conducting clinical trials involving antibody injections that target the receptors of IL-4 and IL-13 simultaneously, and preliminary results indicate that blocked interleukin signaling effectively reduces severe allergic reactions and improves lung function. However, such treatments require repeated injections over a person’s lifetime. Therefore, improvements in alternative treatments are needed.
Researchers developed vaccines targeting interleukin-4 and -13 to treat severe asthma in mice.
Image Source: Diana Polekhina
Researchers from Sorbonne University in France have developed a vaccine that targets IL-4 and IL-13 to treat asthma marked by type 2 inflammation. Vaccines provide immunity against a specific pathogen by activating acquired immunity and proming antibody production against a specific molecule or protein. The scientists administered vaccines that targeted IL-4, IL-13, or both IL-4 and IL-13 in mouse models of asthma. The vaccines effectively induced the production of antibodies against IL-4 and IL-13. Both vaccinated and unvaccinated mice were then exposed to house dust mite (HDM) extract, one of the main allergens contributing to human asthma, and tested for eosinophil numbers, a type of white blood cell that contributes to inflammation. All vaccinated mice had lower eosinophil numbers than unvaccinated mice, with the dual IL-4/IL-13 vaccine causing the greatest reduction in eosinophil numbers in both lung fluid and lung tissue. Additionally, the dual vaccine was able to reduce mucus production and hypersecretion.
To confirm the efficacy of the vaccines on human IL-4 and IL-13, the researchers genetically engineered mice by replacing murine IL-4 and IL-13 with human IL-4 (hIL-4) and human IL-13 (hIL-13). Elevated amounts of immunoglobulin E (IgE), an antibody that causes allergic reactions, as well as mast cells, another immune cell, are characteristic of human allergic asthma. Vaccination against hIL-4 and hIL-13 produced the appropriate antibodies to target the interleukins and reduce IgE levels and mast cell numbers in the lung tissue of HDM-exposed mice. Notably, the IgE and mast cell decreases were localized to just the lungs and remained at basal levels in the skin. Thus, the vaccines only showed significant effects in the lungs (the target area).
Altogether, the combined IL-4 and IL-13 vaccines were effective in treating and preventing severe type 2 asthma in mice models. The researchers believe that these results can be translated to humans suffering from severe asthma, but further research needs to be conducted to ensure the safety and efficacy of the vaccines when given to humans.
To confirm the efficacy of the vaccines on human IL-4 and IL-13, the researchers genetically engineered mice by replacing murine IL-4 and IL-13 with human IL-4 (hIL-4) and human IL-13 (hIL-13). Elevated amounts of immunoglobulin E (IgE), an antibody that causes allergic reactions, as well as mast cells, another immune cell, are characteristic of human allergic asthma. Vaccination against hIL-4 and hIL-13 produced the appropriate antibodies to target the interleukins and reduce IgE levels and mast cell numbers in the lung tissue of HDM-exposed mice. Notably, the IgE and mast cell decreases were localized to just the lungs and remained at basal levels in the skin. Thus, the vaccines only showed significant effects in the lungs (the target area).
Altogether, the combined IL-4 and IL-13 vaccines were effective in treating and preventing severe type 2 asthma in mice models. The researchers believe that these results can be translated to humans suffering from severe asthma, but further research needs to be conducted to ensure the safety and efficacy of the vaccines when given to humans.
Featured Image Source: Towfiqu barbhuiya
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