Abstract
Fasciola hepatica is helminth parasite found around the world that causes fasciolosis, a chronic disease affecting mainly cattle, sheep, and occasionally humans. Triclabendazole is the drug of choice to treat this parasite. However, the continuous use of this drug has led to the development of parasite resistance and, consequently, the limitation of its effectiveness. Hence, vaccination appears as an attractive option to develop. In this work, we evaluated the potential of F. hepatica Kunitz-type molecule (FhKTM) as an antigen formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate ester (Coa-ASC16) and the synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) during an experimental model of fasciolosis in mice, and we further dissected the immune response associated with host protection. Our results showed that immunization of mice with FhKTM/CpG-ODN/Coa-ASC16 induces protection against F. hepatica challenge by preventing liver damage and improving survival after F. hepatica infection. FhKTM/CpG-ODN/Coa-ASC16-immunized mice elicited potent IFN-γ and IL-17A with high levels of antigen-specific IgG1, IgG2a, and IgA serum antibodies. Strikingly, IL-17A blockade during infection decreased IgG2a and IgA antibody levels as well as IFN-γ production, leading to an increase in mortality of vaccinated mice. The present study highlights the potential of a new vaccine formulation to improve control and help the eradication of F. hepatica infection, with potential applications for natural hosts such as cattle and sheep.
Highlights
Fasciolosis is a zoonotic and chronic disease caused by a helminth parasite, F. hepatica, that causes huge economic losses in animal production worldwide
We evaluated the potential of an FhKTM peptide formulated in a nanostructure based on CpG-ODN/Coa-ASC16 as a vaccine during an experimental model of fasciolosis in mice and we further dissected the immune response associated with host protection
FhKTM/CpG-ODN/Coa-ASC16 Vaccination Protects Against F. hepatica Infection
Summary
Fasciolosis is a zoonotic and chronic disease caused by a helminth parasite, F. hepatica, that causes huge economic losses in animal production worldwide. Over the last 25 years, there have been numerous attempts to formulate a successful vaccine against F. hepatica by using parasite extracts or individual antigens [14, 15] These formulations achieved different levels of protection in experimental models of mice, rats, sheep, and cattle [1, 16, 17] by the induction of an antibody response and/or Th1/Th17-mediated cellular immunity [18,19,20,21,22]. We evaluated the potential of an FhKTM peptide formulated in a nanostructure based on CpG-ODN/Coa-ASC16 as a vaccine during an experimental model of fasciolosis in mice and we further dissected the immune response associated with host protection
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