Landmark asthma vaccine looks to human trials
A new article in the journal Nature Communications is reporting successful results from preclinical tests for a unique asthma vaccine. The results indicate the vaccine generates antibodies against the inflammatory molecules known to cause severe asthma and the researchers are now looking to first-phase human clinical trials.
Asthma is a very heterogeneous disease, so beyond treating an acute flare-up with inhaled corticosteroids there are big challenges in developing a universal treatment. A characteristic response seen in about 50 percent of asthma patients is excessive production in the airways of two inflammatory molecules, IL-4 and IL-13.
Blocking the actions of these two inflammatory molecules has been shown to decrease the rate of severe asthma flare-ups and improve lung function. In fact, a treatment called dupilumab has been developed to do exactly that.
Dupilumab is a monoclonal antibody treatment designed to block IL-4 and IL-13 signaling. It was approved for use in moderate-to-severe cases of asthma in 2018 but it suffers several limitations as a long-term therapy. Monoclonal antibody therapies are notoriously expensive, costing thousands of dollars per dose and need consistent dosing to treat chronic disease.
The new research describes the development of a vaccine designed to induce the body to make its own antibodies against IL-4 and IL-13 molecules. The researchers designed what is called a conjugate vaccine, which binds a weak antigen with a strong antigen in order to induce antibodies against the weak antigen. In this instance the experimental asthma vaccine couples the two IL molecules with a non-pathogenic toxin.
In a recently published study the researchers describe several successful preclinical tests of this asthma vaccine. Using mouse models of asthma the researchers demonstrate the vaccine produces antibodies against IL-4 and IL-13 up to a year after immunization. The study also showed the vaccine reducing asthma symptoms in experiments modeling acute allergic flare-ups.
One question that needs to be resolved before the vaccine can move into wider human testing is what kind of effect inhibiting IL-4 and IL-13 activity has on long-term immune responses. Dupilumab, which blocks IL-4 and IL-13 activity, is still a relatively new therapy but there is clinical evidence of patients being safely treated for up to two years with the monoclonal antibody.
This suggests a vaccine offering long-term inhibition of those immune molecules is feasible and potentially safe. However, cautious assessments over the coming years will be needed before this vaccine can be broadly administered.
If subsequent clinical trials for this vaccine prove safe and successful it is hard to understate how significant the treatment would be for millions of asthma sufferers around the world. As well as serving as a both a prophylactic vaccine for asthma and a therapeutic treatment, the researchers suggest this kind of vaccine could be effective against many other allergic diseases underpinned by the same inflammatory molecules.
“Dual vaccination could protect against key features of chronic asthma after both prophylactic or therapeutic vaccination protocols,” the researchers conclude in the new study. “These results pave the way for the clinical development of an efficient long-term vaccine against asthma and other IL-4- and IL-13-mediated allergic diseases, such as food allergies, atopic dermatitis, or chronic urticaria.”
The new study was published in the journal Nature Communications.
Source: Institut Pasteur