A Vaccine Based on Kunitz-Type Molecule Confers Protection Against Fasciola hepatica Challenge by Inducing IFN-g and Antibody Immune Responses Through IL-17A Production

SILVANE LEONARDO; CELIAS, DAIANA PAMELA; ROMAGNOLI P; BELKYS MALETTO; FERNANDA SANCHEZ VALLECILLOS; LAURA CHIAPELLO; SANTIAGO PALMA; DANIEL ALLEMANDI; RODRIGO SANABRIA; CESAR PRUZZO; CRISTINA MOTRAN; CERVI, LAURA

Frontiers in Immunology

Frontiers Media SA

Año: 2020

Fasciola hepatica is helminth parasite found around the world that causes fasciolosis, achronic disease affectingmainly cattle, sheep, and occasionally humans. Triclabendazoleis the drug of choice to treat this parasite. However, the continuous use of thisdrug has led to the development of parasite resistance and, consequently, thelimitation of its effectiveness. Hence, vaccination appears as an attractive optionto develop. In this work, we evaluated the potential of F. hepatica Kunitz-typemolecule (FhKTM) as an antigen formulated with a liquid crystal nanostructure formedby self-assembly of 6-O-ascorbyl palmitate ester (Coa-ASC16) and the syntheticoligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN)during an experimental model of fasciolosis in mice, and we further dissected theimmune response associated with host protection. Our results showed that immunizationof mice with FhKTM/CpG-ODN/Coa-ASC16 induces protection against F. hepaticachallenge by preventing liver damage and improving survival after F. hepatica infection.FhKTM/CpG-ODN/Coa-ASC16-immunized mice elicited potent IFN-g and IL-17A withhigh levels of antigen-specific IgG1, IgG2a, and IgA serum antibodies. Strikingly, IL-17Ablockade during infection decreased IgG2a and IgA antibody levels as well as IFN-gproduction, leading to an increase in mortality of vaccinated mice. The present studyhighlights the potential of a new vaccine formulation to improve control and help theeradication of F. hepatica infection, with potential applications for natural hosts such ascattle and sheep.