Abstract
Fasciolosis is considered the most widespread trematode disease affecting grazing animals around the world; it is currently recognised by the World Health Organisation as an emergent human pathogen. Triclabendazole is still the most effective drug against this disease; however, resistant strains have appeared and developing an effective vaccine against this disease has increasingly become a priority. Several bioinformatics tools were here used for predicting B- and T-cell epitopes according to the available data for Fasciola hepatica protein amino acid sequences. BALB/c mice were immunised with the synthetic peptides by using the ADAD vaccination system and several immune response parameters were measured (antibody titres, cytokine levels, T-cell populations) to evaluate their ability to elicit an immune response. Based on the immunogenicity results so obtained, seven peptides were selected to assess their protection-inducing ability against experimental infection with F. hepatica metacercariae. Twenty-four B- or T-epitope-containing peptides were predicted and chemically synthesised. Immunisation of mice with peptides so-called B1, B2, B5, B6, T14, T15 and T16 induced high levels of total IgG, IgG1 and IgG2a (p<0.05) and a mixed Th1/Th2/Th17/Treg immune response, according to IFN-γ, IL-4, IL-17 and IL-10 levels, accompanied by increased CD62L+ T-cell populations. A high level of protection was obtained in mice vaccinated with peptides B2, B5, B6 and T15 formulated in the ADAD vaccination system with the AA0029 immunomodulator. The bioinformatics approach used in the present study led to the identification of seven peptides as vaccine candidates against the infection caused by Fasciola hepatica (a liver-fluke trematode). However, vaccine efficacy must be evaluated in other host species, including those having veterinary importance.
Highlights
Fasciolosis is one of the most important helminthiasis worldwide affecting grazing livestock due its widespread geographical distribution and resulting economic loss; it is caused by the common liver fluke Fasciola hepatica, along with the related species Fasciola gigantica [1]
Taking into account that peptides used for immunisation were synthesised adding a glycine and a cysteine at both termini and polymerised inducing the formation of disulphide bridges, the presence of any additional cysteine residue in a monomersynthesised peptide could lead to several polymerised forms being obtained from the peptide
Other studies have shown the importance of two F. hepatica cathepsins (FheCB and FheCL), expressed in the infective stage of newly excysted juveniles (NEJs), in acquiring infection
Summary
Fasciolosis is one of the most important helminthiasis worldwide affecting grazing livestock due its widespread geographical distribution and resulting economic loss; it is caused by the common liver fluke Fasciola hepatica, along with the related species Fasciola gigantica [1]. Taking its impact on human health and wide emergence into account, human fasciolosis has been recently included in the World Health Organization’s (WHO) list of priorities related to Neglected Tropical Diseases [4]. It is well-known that methodological and technical difficulties related to diagnosis have limited progress in combating human fasciolosis globally, including drawbacks in diagnosing infection and assessing drug efficacy and resistance, mainly concerning triclabendazole which is still the most effective drug for combating the disease. The aforementioned research challenge must involve identifying new target antigens for obtaining an effective vaccine against F. hepatica [7]
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