Vacuna nanoparticulada basada en un inhibidor de proteasas de tipo kunitz protege contra la infección por Fasciola hepatica, a través de un mecanismo dependiente de IL-17 y anticuerpos.

SILVANE L; ROMAGNOLI P; SANABRIA RODRIGO; . CERVI L.; CELIAS D; PALMA SD; PRUZZO CESAR; MALETTO B; ALLEMANDI DA; MOTRAN C.C.

Tucuman

Congreso; LXVII Reunión Anual de la Sociedad Argentina de Inmunología; 2019

Sociedad Argentina de Inmunología

F.hepatica is a helminth that causes a chronic disease mainly in cattle, sheep and occasionally in humans. The limitations of chemotherapy have led to the development of vaccines to protect against F.hepatica infection. Kunitz type molecule (Fh-KTM) is a highly expressed protein in the parasite and plays a vital role in its survival.In this work we evaluate the mechanisms by which Fh-KTM formulated with a liquid crystal nanostructure (CpG-ODN/Coa-ASC16) induces protection against this parasite.BALB/c mice were weekly immunized for 3 weeks with Fh-KTM/CpG-ODN/Coa-ASC16, CpG-ODN/Coa-ASC16 alone or saline. One week after last immunization the mice were orally challenge with F. hepatica metacercariae.The vaccinated mice group showed significantly improved survival rates (p> 0.05 Mantel-Cox Test) compared with CpG-ODN/Coa-ASC16 immunized and the infected control. In correlation, liver damage and transaminase enzymes exhibited reduced levels in vaccinated mice. Besides, Fh-KTM/CpG-ODN/Coa-ASC16 vaccinated mice also showed high levels of specific IgG1, IgG2a and IgA in serum (p >0.05 ANOVA) compared with another groups. In addition, IgA titers were increased in intestinal lavage and feces (p>0.05 ANOVA). Systemic IL-17 and IFN-γ cytokines levels were higher in vaccinated mice (p >0.05 ANOVA) than in the other groups.The neutralizing treatment of IL-17 in vaccinated mice decreased IgG2a and IgA antibody levels as well as IFN-γ production (p> 0.05 ANOVA). Remarkably, the IL-17 neutralization led to an increase in the mortality of vaccinated mice.These results indicate that IL-17 production is a key event for the protective mechanisms against F.hepatica through the IFN-γ and antibodies secretion.