title: In vitro and in vivo studies for assessing the immune response and protection-inducing ability conferred by Fasciola hepatica-derived synthetic peptides containing B- and T-cell epitopes.
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.
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Salamanca, Spain; Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia.
authors.forename: Jose
authors.initials: J
authors.lastname: Rojas-Caraballo
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Salamanca, Spain.
authors.forename: Julio
authors.initials: J
authors.lastname: López-Abán
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Salamanca, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: Pérez del Villar
authors.affiliation: Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia.
authors.forename: Carolina
authors.initials: C
authors.lastname: Vizcaíno
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Salamanca, Spain.
authors.forename: Belén
authors.initials: B
authors.lastname: Vicente
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Salamanca, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Fernández-Soto
authors.affiliation: Pharmaceutical Chemistry Department, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Salamanca, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: del Olmo
authors.affiliation: Molecular Biology and Immunology Department, Fundación Instituto de Inmunología de Colombia (FIDIC), Bogotá, Colombia; Basic Sciences Department, School of Medicine and Health Sciences, Universidad del Rosario, Bogotá, Colombia.
authors.forename: Manuel Alfonso
authors.initials: MA
authors.lastname: Patarroyo
authors.affiliation: Parasite and Molecular Immunology Laboratory, Tropical Disease Research Centre, Universidad de Salamanca (IBSAL-CIETUS), Salamanca, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Muro
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000909:Antibodies, Helminth / Q000097:blood / Q000276:immunology; D016000:Cluster Analysis; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D018985:Epitopes, B-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000737:chemistry / Q000276:immunology*; D005210:Fasciola hepatica / Q000737:chemistry* / Q000276:immunology*; D005211:Fascioliasis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000401:mortality / Q000469:parasitology / Q000517:prevention & control; D005260:Female; D020869:Gene Expression Profiling; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D010455:Peptides / Q000138:chemical synthesis / Q000276:immunology*; D016052:Protozoan Vaccines / Q000276:immunology
chemical_list: D000909:Antibodies, Helminth; D016207:Cytokines; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; D010455:Peptides; D016052:Protozoan Vaccines