Dual vaccination against IL-4 and IL-13 protects against chronic allergic asthma in mice

Abstract

Allergic asthma is characterized by elevated levels of IgE antibodies, type 2 cytokines such as interleukin-4 (IL-4) and IL-13, airway hyperresponsiveness (AHR), mucus hypersecretion and eosinophilia. Approved therapeutic monoclonal antibodies targeting IgE or IL-4/IL-13 reduce asthma symptoms but require costly lifelong administrations. Here, we develop conjugate vaccines against mouse IL-4 and IL-13, and demonstrate their prophylactic and therapeutic efficacy in reducing IgE levels, AHR, eosinophilia and mucus production in mouse models of asthma analyzed up to 15 weeks after initial vaccination. More importantly, we also test similar vaccines specific for human IL-4/IL-13 in mice expressing human IL-4/IL-13 and the related receptor, IL-4Rα, to find efficient neutralization of both cytokines and reduced IgE levels for at least 11 weeks post-vaccination. Our results imply that dual IL-4/IL-13 vaccination may represent a cost-effective, long-term therapeutic strategy for the treatment of allergic asthma as demonstrated in mouse models, although additional studies are warranted to assess its safety and feasibility.

Development and preclinical evaluation of a vaccine targeting IL‐4 and IL‐13 for the treatment of allergic asthma

“…Unlike therapeutic mAbs, this effect is long-lasting, representing a clear benefit for the treatment of chronic diseases. These findings were published recently 9 and, now, need to be confirmed in clinical trials. Interestingly, a kinoid targeting interferon alpha (IFNα) was recently tested in a phase 2b study in 185 adults with active systemic lupus erythematosus.…”

Codonopsis laceolata Water Extract Ameliorates Asthma Severity by Inducing Th2 Cells’ and Pulmonary Epithelial Cells’ Apoptosis via NF-κB/COX-2 Pathway

“…IL-13 could stimulate asthma via various effects such as IgE secretion, eosinophilia stimulation, mucous hypersecretion, and airway remodeling via the NF-κB pathway [44,45]. Because of the importance of the inhibition effect of IL-4 and IL-13 against asthma occurrence, research for a dual vaccination of anti-IL-4 and anti-IL-13 against asthma has increased [46]. C. laceolata treatment effectively suppressed the expression of IL-4 and IL-13 via down-regulating GATA-3 levels (Figure 3), which means that if the antiasthmatic potency of C. laceolata could be very high, there is the potential for C. laceolata to be a new anti-asthmatic agent.…”

Targeting TL1A/DR3 Signaling Offers a Therapeutic Advantage to Neutralizing IL13/IL4Rα in Muco-Secretory Fibrotic Disorders

“…IL4 is involved in regulating T cell proliferation and survival, and IgE synthesis. In contrast, IL-13 is predominantly involved in airway remodeling and mucus hypersecretion (12)(13)(14). Several lines of evidence support the contention that IL13, and not IL4, controls mucus production in asthma.…”

“…Additionally, IL4-deficient Th2 cells adoptively transferred to mice receiving inhaled ovalbumin failed to enhance mucus production by their bronchial epithelium (18). Furthermore, conjugate vaccines against IL4 failed to reduce mucus production in murine model of asthma induced by HDM, as opposed to ones directed against IL13 that abrogated mucus production in the lung bronchial epithelium (14). Collectively this data indicates IL4 is unable to mount a muco-secretory phenotype independently of IL13.…”