Toxoplasma gondii serine-protease inhibitor-1: a novel vaccine candidate for asthma treatment

ARIADNA SOTO; IGNACIO FENOY; VANESA SÁNCHEZ; MARÍA ALDIRICO; MATÍAS PERRONE SIBILIA; MARIANO PICCHIO; NADIA ARCÓN; PATRICIO ACOSTA; VALENTINA MARTÍN; ALEJANDRA GOLDMAN

Melbourne

Congreso; International Congress of Immunology; 2016

Serine proteases are important players in the pathogenesis of asthma, promoting inflammation and tissue remodeling. In addition, some allergens have serine protease activity. It?s known that many serine protease inhibitors display immunomodulatory properties. TgPI-1 is a Toxoplasma gondii protein that exhibits broad spectrum inhibitory activity against serine proteases. We sought to investigate whether rTgPI-1 administration could suppress experimental asthma. BALB/c mice were intraperitoneally sensitized with ovalbumin/alum and airway-challenged. Once the asthmatic phenotype was achieved they were intranasally treated with different doses of rTgPI-1 alone (PI) or co-administrated with ovalbumin (OPI). Treatment with PI and OPI reduced 13.8% and 50.3% the airway hyperresponsiveness, respectively. This effect was accompanied by a diminished bronchoalveolar eosinophilia, mucus production and peribronchial lung infiltration. Moreover, bronchoalveolar lavage fluid from treated mice showed a reduction in IL-4 and IFN-γ levels. In agreement with these results, both treatments resulted in lower levels of IL-4, IL-5 and IFN-γ in thoracic lymph node cells stimulated with ovalbumin. Regulatory IL-10 was also diminished. Furthermore, OPI induced a reduction in ovalbumin specific T cell proliferation. Treatment did not alter ovalbumin-specific humoral response. These results show that both rTgPI-1 treatments reduced asthma hallmarks; however, OPI was more effective denoting an adjuvant capacity. The effect of rTgPI-1 in modulating allergic lung inflammation could be the consequence of a decrease in the overall local response to the allergen. Although further studies should be undertaken to completely elucidate the mechanisms involved, TgPI-1 is a promising therapeutic vaccine candidate for intervention in patients with asthma.