Late Breaking Abstract - Anti-IL-4 and anti-IL-13 dual vaccination using Kinoid technology prevents development of allergic asthma in mice

Allergic asthma is considered as a consequence of a tolerance breakdown, resulting in type 2 immune responses characterized by overproduction of cytokines such as IL-4 and IL-13. IL-4/IL-13 kinoids are vaccines consisting of mouse IL-4 and IL‑13 molecules coupled to a non-toxic diphtheria toxin mutant, serving as a carrier protein. Immunizations with these kinoids elicit the production of polyclonal anti-IL-4/IL-13 neutralizing antibodies. We aimed to evaluate the benefit of IL-4/IL-13 kinoids in a mouse model of allergic asthma induced by repeated intranasal administrations of house dust mite. This model recapitulates the main clinical hallmarks of asthma such as chronic airway inflammation, mucus production and airway hyperreactivity (AHR). To assess the effect of kinoid vaccination, mice received four intramuscular injections of IL-4 kinoid (IL-4-K), IL-13 kinoid (IL-13-K) or a combination of both (combo-K). Respiratory functions were evaluated by plethysmography, airway and lung inflammation by histology or flow cytometry, mucus production by histology and antibody production by ELISA and cellular bioassays. High titers of anti-IL-4 and/or IL-13 neutralizing antibodies were detected in sera from kinoid-immunized mice. AHR, airway and lung eosinophilia, mucus production and IgE levels were partially reduced in mice vaccinated with IL-4-K or IL-13-K. Combo-K vaccination, however, protected mice from all these features of allergic asthma. Our results demonstrate that kinoids are capable to break B cell tolerance against IL-4 and IL-13, and protect mice from allergic airway inflammation, representing a promising new therapeutic strategy for the treatment of asthma.