Fasciola hepatica vaccine based on Kunitz-Type Molecule reduces adult worm fecundity in experimentally infected sheep

Background Fasciolosis is a cosmopolitan and continuously expanding helmintiasis produced by the trematode Fasciola hepatica. Globally, sheep and cattle are the main definitive hosts of F. hepatica. The economic losses caused by this disease in livestock production are calculated to be around US$ 3 billion annually. The reports of resistance to anthelmintics described in F. hepatica highlight the urgent need to develop an effective vaccine that reduce the impact and spread of the disease through a reduction in the number of eggs and their viability, as well as a decrease in the number of adults to allow a reduction in liver damage
Methods Sheep were immunized with two doses, administered 21 days apart, of the F. hepatica Kunitz-type molecule (sFhKT) vaccine, formulated with a liquid crystal nanostructure composed of 6-O-ascorbyl palmitate ester (Coa-ASC16) and synthetic oligodeoxynucleotides containing unmethylated cytosine-guanine motifs (CpG-ODN), and were subsequently infected with 100 metacercariae. Thirty days after the number of worms in the bile canaliculi and gallbladder, as well as the egg count and viability in feces, were determined. Sheep-specific anti-IgG antibodies for sFhKT were measured by ELISA
Results The sFhKT/CpG-ODN/Coa-ASC16 vaccine formulation with the highest sFhKT dose was the most effective, significantly reducing fecal egg counts (FEC) by 81.6%. It also reduced worm burden by 55.7%, although this difference was not statistically significant. The addition of Cathepsin L3 (FhCL3) to the formulation further reduced FEC (89.1%) but resulted in a lower reduction in worm burden. Sheep vaccinated with sFhKT/CpG-ODN/Coa-ASC16 exhibited slightly less hepatic damage than non-vaccinated animals, with histological lesions characterized by increased inflammatory infiltrates. The experimental vaccine FhKT/CpG-ODN/Coa-ASC16 induced an IgG antibody response with higher titers in immunized sheep compared to those that did not receive the vaccine, although the difference was not statistically significant.
Conclusions In this study, sFhKT/CpG-ODN/Coa-ASC16 was evaluated as a vaccine candidate against F. hepatica in sheep. The significant reduction in worm fertility in vaccinated animals suggests the possibility of continuing with further investigations that could improve the efficacy of the proposed vaccine .