The cytokines interleukin-4 (IL-4) and IL-13 play important, nonredundant roles in the pathogenesis of asthma. Monoclonal antibodies against IL-4 receptor α (IL-4Rα), which inhibit both IL-4 and IL-13 signaling, can effectively ameliorate severe asthmatic exacerbations. However, monoclonal antibody therapy is expensive and requires regular injections. Conde et al. developed conjugate vaccines (“kinoids”) against IL-4 and IL-13 by coupling these cytokines with a nontoxic mutant of diptheria toxin. These kinoids were effective as both prophylactics and therapeutics in mouse models of allergic airway inflammation, durably reducing hallmarks of disease including serum immunoglobulin E, airway hyperresponsiveness, and mucus hypersecretion. Similar results were obtained with transgenic mice expressing human IL-4, IL-13, and IL-4Rα. Thus, dual IL-4/IL-13 vaccination may be a long-lasting and economical approach to the treatment of asthma and other allergic diseases.
Nat. Commun. 12, 2574 (2021).