Moderate protection is induced by a chimeric protein composed of leucine aminopeptidase and cathepsin L1 against Fasciola hepatica challenge in sheep

• Published in: Vaccine Vol. 37; no. 24; pp. 3234 - 3240
• Main Authors: Ortega-Vargas, S., Espitia, C., Sahagún-Ruiz, A., Parada, C., Balderas-Loaeza, A., Villa-Mancera, A., Quiroz-Romero, H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 27.05.2019; Elsevier Limited
• Subjects: Aminopeptidase; Animals; Antigens; Cattle; Chimeric protein; Conflicts of interest; Excretion; Fasciola hepatica; IgG antibody; Immunization; Immunoglobulin G; Immunoglobulins; Infections; Isotypes; Leucine; Lymphocytes T; Migration; Ovis aries; Parasites; Proteins; Sheep; Vaccines; United States > US; Fasciola hepatica; Sheep; Immunization; Chimeric protein
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2019.04.067

•A chimeric protein was evaluated against challenge of F. hepatica in sheep.•The highest level of protection achieved with the chimeric protein was 46.51%.•A significant reduction in the egg output of F. hepatica was observed in vaccinated sheep.•High rFhLAP-CL1-specific IgG1 and IgG2 levels suggest a mixed Th1/Th2 response. Leucine aminopeptidase (FhLAP) and cathepsin L1 (FhCL1) of Fasciola hepatica play a critical role in parasite feeding, migration through host tissue, and immune evasion. These antigens have been tested for immune protection as single components with variable degrees of success. The chimeric-protein approach could improve protection levels against fasciolosis. Previously, we reported the design and construction of a chimeric protein composed of antigenic sequences of FhLAP and FhCL1 of F. hepatica. The goal of the present study was to express and evaluate the immune-protective capacity of this chimeric protein (rFhLAP-CL1) in sheep. Animals were randomly allocated into five groups with five animals in each group. Groups 1, 2 and 3 were immunized twice with 100 μg, 200 μg and 400 μg of rFhLAP-CL1 emulsified with Quil A adjuvant, whereas groups 4 and 5 were the adjuvant control and infection control groups, respectively. The animals were then challenged with 200 metacercariae two weeks after the rFhLAP-CL1 booster. The fluke burden was reduced by 25.5%, 30.7% (p < 0.05) and 46.5% (p < 0.01) in sheep immunized with 100 μg, 200 μg and 400 μg of chimeric protein, respectively, in comparison to the infection control group. There was a reduction of 22.7% (p < 0.05) and 24.4% (p < 0.01) in fecal egg count in groups 2 and 3, respectively, compared to the infection control group. Sheep immunized with chimeric protein produced F. hepatica excretion-secretion product-specific total IgG antibody, which were increased after challenge. Moreover, the levels of rFhLAP-CL1-specific IgG1 and IgG2 isotypes in immunized sheep increased rapidly two weeks after the first immunization and were significantly more elevated than those of the control groups, indicating a mixed Th1/Th2 response. This is a preliminary evaluation of the chimeric protein rFhLAP-CL1 as a possible immunogen against F. hepatica infection in sheep.