Abstract
BackgroundFasciolosis is one of the most important parasitic diseases of livestock. The need for better control strategies gave rise to the identification of various vaccine candidates. The recombinant form of a member of the cysteineprotease family, cathepsin L1 of Fasciola hepatica (FhCL1) has been a vaccine target for the past few decades since it has been shown to behave as an immunodominant antigen. However, when FhCL1 was used as vaccine, it has been observed to elicit significant protection in some trials, whereas no protection was provided in others.MethodsIn order to improve vaccine development strategy, we conducted a linear B-cell epitope mapping of FhCL1 in sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus Montanide and with significant reduction of the fluke burden, sheep vaccinated with FhCL1, FhHDM, FhLAP and FhPrx plus aluminium hydroxide and with non-significant reduction of the fluke burden, and in unvaccinated-infected sheep.ResultsOur study showed that the pattern and dynamic of peptide recognition varied noticeably between both vaccinated groups, and that the regions 55–63 and 77–84, which are within the propeptide, and regions 102–114 and 265–273 of FhCL1 were specifically recognised only by vaccinated sheep with significant reduction of the fluke burden. In addition, these animals also showed significant production of specific IgG2, whereas a scarce non-significant production was observed in animals vaccinated with Aluminium hydroxide and no production was detected in infected control animals. ConclusionsWe have identified 42 residues of FhCL1 that contributed to protective immunity against infection with F. hepatica in sheep. Our results provide indications in relation to key aspects of the immune response. Given the variable outcomes of vaccination trials conducted in ruminants to date, this study adds new insights to improve strategies of vaccine development.
Highlights
Fasciolosis is one of the most important parasitic diseases of livestock
Vaccine preparation Two different vaccine formulations were prepared using recombinant forms of F. hepatica cathepsin L1 (FhCL1), F. hepatica helminth defence molecule (FhHDM), F. hepatica leucine aminopeptidase (FhLAP) and F. hepatica peroxiredoxin (FhPrx), which were combined with either Montanide or aluminium hydroxide (Alum) adjuvants
Parasitological results When data from vaccinated groups (G1-group 2 (G2)) were compared to that obtained in the control group (G3), a statistically significant protection of 37.3% for group 1 (G1) and a non-significant protection of 13.8% for G2 was observed, in terms of reduction of the liver fluke burden
Summary
Fasciolosis is one of the most important parasitic diseases of livestock. The need for better control strat‐ egies gave rise to the identification of various vaccine candidates. Buffoni et al Parasites Vectors (2020) 13:390 for a vaccine to better control the disease gave rise to the identification of various potential vaccine candidates. These have been assessed over the past few decades with contrasting results in terms of their efficacy in producing protective immunity against infection. The difficulty in producing an effective vaccine is compounded by the immunomodulatory capacity of various Fasciola hepatica antigens, as has been extensively reported. This immunomodulation includes suppression of dendritic cell maturation and function [2], activation of a suppressive dendritic cell population which weakens Th17 cells [3], induction of T cell anergy [4] and impairment of mast cells to drive Th1 responses [5]
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