Active Immunization against Interleukin-4 Suppresses Allergic Airway Inflammation in A Mouse Model Induced by House Dust Mite Extracts
Gao Ruiyu, Yan Jiao, Yuan Mingcui, Ma Yanbing*
Asthma is featured by Th2 dominated inflammatory responses which mainly driven by IL-4. This study was purposed to evaluate the efficacy of active immunization against IL-4 in a mouse model of allergic airway inflammation. By using gene recombinant techniques, a vaccine presenting IL-4 antigen epitope on the surface and in the immune-dominant domain of hepatitis B virus core antigen (HBcAg) virus-like particle (VLP) were constructed. The recombinant protein HBcAg/IL-4 was expressed by induction with IPTG, and then purified by a procedure consists of ammonium sulfate precipitation and sucrose density gradient centrifugation. The VLPs structure was further identified with electron microphotographic techniques. Mice were immunized with vaccine 3 times at 2 week intervals before the repeated sensitization and challenge with house dustmite extracts (HDM). The numbers of total inflammatory cells and eosinophils in BALF((bronchoalveolar lavage fluid for lung cancer) were counted. The level of IL-4, IL-5, IL-13 and IFN-γ was measured and the IL-4 -specific IgG and HBcAg-specific IgG1 and IgG2a responses were analyzed using ELISA. The airway and lung tissue mechanics were measured using flexiVent. In the mice immunized with the immunization with recombinant HBcAg/IL-4 VLP vaccine, the IL-4-specific IgG was induced and maintained at high level through the experiment; the infiltrated airway inflammatory cells, especially eosinophils, as well as the levels of Th2 cytokines IL-4, IL-5 and IL-13 in BALF, were significantly reduced; the HBcAg-specific IgG1 response was suppressed significantly whereas IgG2a response was elevated; in addition, airway hyperresponsiveness was significantly ameliorated. Active immunization with a VLP vaccine targeting IL-4 significantly suppressed HDM-induced airway inflammatory responses, providing a potential approach for the study on immune-pathogenic mechanisms and immunotherapeutic intervention of asthma.
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