Current therapeutic approaches to
asthma have had limited impact on the clinical management and resolution of this disorder. By using a novel
vaccine strategy targeting the inflammatory
cytokine IL-5, we have ameliorated hallmark features of
asthma in mouse models. Delivery of
a DNA vaccine encoding murine
IL-5 modified to contain a promiscuous foreign Th
epitope bypasses B cell tolerance to
IL-5 and induces neutralizing polyclonal anti-IL-5 Abs. Active vaccination against
IL-5 reduces airways
inflammation and prevents the development of
eosinophilia, both hallmark features of
asthma in animal models and humans. The reduced numbers of inflammatory T cells and eosinophils in the lung also result in a marked reduction of Th2
cytokine levels. Th-modified
IL-5 DNA vaccination reduces the expression of
IL-5 and
IL-4 by approximately 50% in the airways of
allergen-challenged mice. Most importantly, Th-modified
IL-5 DNA vaccination restores normal bronchial hyperresponsiveness to beta-
methacholine. Active vaccination against
IL-5 reduces key pathological events associated with
asthma, such as Th2
cytokine production, airways
inflammation, and hyperresponsiveness, and thus represents a novel therapeutic approach for the treatment of
asthma and other allergic conditions.