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    Respir Res. 2009 Jun 16;10:51.

    Ag85B DNA vaccine suppresses airway inflammation in a murine model of asthma.

    Wu J, Xu J, Cai C, Gao X, Li L, Zhong N.

    Department of Respiratory Disease, Peking University First Hospital, Beijing, PR China. wjxst@hotmail.com

    BACKGROUND: In allergic asthma, Th2 lymphocytes are believed to play important roles in orchestrating airway eosinophilia and inflammation. Resetting the Th1/Th2 imbalance may have a therapeutic role in asthma. The mycobacterium tuberculosis 30-kilodalton major secretory protein (antigen 85B, Ag85B) can protect animals from M. tuberculosis infection by inducing a Th1-dominant response. METHODS: In this study, the Ag85B gene was cloned into pMG plasmids to yield the pMG-Ag85B plasmid. The expression of Ag85B gene in murine bronchial epithelia cells was detected by Western blotting and immunohistochemical staining after intranasal immunization with reconstructed pMG-Ag85B plasmids. The protective effect of pMG-Ag85B plasmids immunization in airway inflammation was evaluated by histological examination and bronchoalveolar lavage (BAL). IL-4 and IFN-gamma levels in the BAL and supernatant from splenocyte culture were determined using ELISA kits. RESULTS: The Ag85B gene was successfully expressed in murine bronchial epithelia cells by intranasal immunization with reconstructed pMG-Ag85B plasmids. Using a murine model of asthma induced by ovalbumin (OVA), pMG-Ag85B immunization significantly inhibited cellular infiltration across the airway epithelium with a 37% decrease in the total number of cells (9.6 +/- 2.6 x 10(5)/ml vs. 15.2 +/- 3.0 x 10(5)/ml, p < 0.05) and a 74% decrease in the number of eosinophils (1.4 +/- 0.2 x 10(5)/ml vs. 5.4 +/- 1.1 x 10(5)/ml, p < 0.01) compared with the OVA-sensitized control group. There was no difference in the number of neutrophils in BAL fluid between the pMG-Ag85B group, the OVA-sensitized control group and the empty pMG group. IL-4 production was significantly decreased in the BAL fluid (32.0 +/- 7.6 pg/ml vs. 130.8 +/- 32.6 pg/ml, p < 0.01) and in the splenocyte supernatant (5.1 +/- 1.6 pg/ml vs. 10.1 +/- 2.3 pg/ml, p < 0.05) in the pMG-Ag85B group compared with the OVA-sensitized control group, while IFN-gamma production was increased in the BAL fluid (137.9 +/- 25.6 pg/ml vs. 68.4 +/- 15.3 pg/ml, p < 0.05) and in the splenocyte supernatant (20.1 +/- 5.4 pg/ml vs. 11.3 +/- 3.2 pg/ml, p < 0.05). CONCLUSION: In a murine model of asthma induced by OVA, intranasal immunization with pMG-Ag85B significantly reduced allergic airway inflammation with less eosinophil infiltration. This protective effect was associated with decreased IL-4 and increased IFN-gamma production in the BAL fluid and in the supernatant of cultured splenocytes.

    PMID: 19531238 [PubMed - indexed for MEDLINE]

    PMCID: PMC2713210

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