Abstract
The liver fluke Fasciola hepatica is an economically important global pathogen of humans and their livestock. To facilitate host invasion and migration, F. hepatica secretes an abundance of cathepsin peptidases but prevents excessive damage to both parasite and host tissues by co-secreting regulatory peptidase inhibitors, cystatins/stefins and Kunitz-type inhibitors. Here, we report a vaccine strategy aimed at disrupting the parasite’s protease/anti-protease balance by targeting these key inhibitors. Our vaccine cocktail containing three recombinant stefins (rFhStf-1, rFhStf-2, rFhStf-3) and a Kunitz-type inhibitor (rFhKT1) formulated in adjuvant Montanide 61VG was assessed in two independent sheep trials. While fluke burden was not reduced in either trial, in Trial 1 the vaccinated animals showed significantly greater weight gain (p < 0.05) relative to the non-vaccinated control group. In both trials we observed a significant reduction in egg viability (36–42%). Multivariate regression analyses showed vaccination and increased levels of IgG2 antibodies specific for the F. hepatica peptidase inhibitors were positive indicators for increased weight gain and levels of haemoglobin within the normal range at 16 weeks post-infection (wpi; p < 0.05). These studies point to the potential of targeting peptidase inhibitors as vaccine cocktails for fasciolosis control in sheep.
Highlights
Helminth parasites have a major impact on global animal production, accounting for greater than 55% of all livestock disease [1,2]
We and others have attempted to protect sheep and cattle against fasciolosis by targeting the parasite cathepsin cysteine peptidases via vaccination programs using either native or recombinant proteins, with variable success [41]
While we observed some significant impacts on weight gain and egg production/viability these were nowhere near the threshold needed for an on-farm vaccine
Summary
Helminth (worm) parasites have a major impact on global animal production, accounting for greater than 55% of all livestock disease [1,2]. One of the most prevalent diseases contributing to the negative impact on sheep and cattle production is caused by the trematode liver fluke parasite, Fasciola hepatica. Fasciolosis, the disease resulting from infection by liver fluke parasites results in major losses of €2.5 billion globally [3]. As well as causing mortality, liver fluke causes subclinical production losses, with a recent meta-analysis estimating that liver fluke infections result in a 9% reduction in daily weight gain [5]. Parasite control is currently reliant on the use of anthelmintic chemicals, with the use of the benzimidazole class drug triclabendazole predominating for anti-fluke treatment [6]
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