Chronic allergic asthma is a well-known immunological disease affecting the lungs, where patients suffer from variable respiratory symptoms (breathing difficulties, chest pain, cough…) due to airflow obstruction. A major molecular mechanism of asthma is type 2 inflammation, which involves production of interleukin-4 (IL-4) and interleukin-13 (IL-13) in the lung, high IgE antibodies levels and airway eosinophilia. As this process occurs in large proportion of patients (~50%), targeting the signaling of both interleukins is considered to minimize the gravity of chronic asthma.
Dual vaccination against IL-4 and IL-13 using kinoids (a conjugate vaccine) is one of the therapeutic strategies suggested to neutralize the response induced by this type 2 inflammation. In recent studies by Conde et al 2021, House Dust Mite (HDM)-treated mice, which exhibit key characteristics of human chronic asthma, were used to test prophylactic and therapeutic dual vaccination efficiency in this allergic mouse model. Using whole body plethysmography, this group demonstrated significant beneficial effects of this dual IL-4/IL-3 vaccination on airway hyperresponsiveness while exposing mice to increasing doses of methacholine (bronchoconstrictor used in human asthma diagnosis). Furthermore, dual vaccinated mice showed a significant improvement in flexiVent lung function such as a decrease in lung resistance and elastance when compared to the PBS-treated control mice. Additionally, dual vaccination induced further reduction of lung tissue eosinophils whereas single vaccination with IL-4 kinoid or IL-13 kinoid alone showed no effect on eosinophil numbers. Dual vaccination decreased all key features of HDM-induced asthma in mice.
Mice humanized for IL-4/IL-13 and vaccinated with dual human-IL-4 and human-IL-13 kinoids also presented a reduction in circulating IgE and membrane-bound IgE on basophils (5 weeks post primary vaccination) meaning an efficient targeting of the human interleukins and their receptor. This argues in favor of developing a long-term effect vaccine against the severity of the type 2 inflammation response in asthma. Overall, results show that targeting mouse and human IL-4 and IL-13 using dual vaccination, strongly lowers major mechanisms exacerbated in chronic asthma.
Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice. Conde, et al. (2021). Nature Communications, 12: 2574