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 areimportant players in the pathogenesis of asthma,promoting inflammation and tissue remodeling. In addition, some allergens haveserine protease activity. It?s known that many serine protease inhibitorsdisplay immunomodulatory properties. TgPI-1 is a Toxoplasma gondii protein that exhibits broad spectrum inhibitoryactivity against serine proteases. We sought to investigate whether rTgPI-1administration could suppress experimental asthma. BALB/c mice were intraperitoneallysensitized with ovalbumin/alum and airway-challenged. Once the asthmaticphenotype was achieved they were intranasally treated with different doses ofrTgPI-1 alone (PI) or co-administrated with ovalbumin (OPI). Treatment with PIand OPI reduced 13.8% and 50.3% the airway hyperresponsiveness, respectively.This effect was accompanied by a diminished bronchoalveolar eosinophilia, mucusproduction and peribronchial lung infiltration. Moreover, bronchoalveolarlavage fluid from treated mice showed a reduction in IL-4 and IFN-γ levels. Inagreement 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. Treatmentdid not alter ovalbumin-specific humoral response. These results show that bothrTgPI-1 treatments reduced asthma hallmarks; however, OPI was more effectivedenoting an adjuvant capacity. The effect of rTgPI-1in modulating allergic lung inflammation could be the consequence of a decreasein the overall local response to the allergen. Although further studies shouldbe undertaken to completely elucidate the mechanisms involved, TgPI-1 is apromising therapeutic vaccine candidate for intervention in patients withasthma.