Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth Fasciola hepatica .

Autor:	Cwiklinski K; Molecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, Ireland.; School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, Belfast BT9 5DL, UK., Drysdale O; School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, Belfast BT9 5DL, UK., López Corrales J; Molecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, Ireland., Corripio-Miyar Y; Moredun Research Institute, Pentland Science Park, Penicuik, Midlothian EH26 0PZ, UK., De Marco Verissimo C; Molecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, Ireland.; School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, Belfast BT9 5DL, UK., Jewhurst H; Molecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, Ireland.; School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, Belfast BT9 5DL, UK., Smith D; School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, Belfast BT9 5DL, UK.; Moredun Research Institute, Pentland Science Park, Penicuik, Midlothian EH26 0PZ, UK., Lalor R; Molecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, Ireland., McNeilly TN; Moredun Research Institute, Pentland Science Park, Penicuik, Midlothian EH26 0PZ, UK., Dalton JP; Molecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, Ireland.; School of Biological Sciences, Medical Biology Centre, Queen's University Belfast, Belfast BT9 5DL, UK.
Jazyk:	angličtina
Zdroj:	Vaccines [Vaccines (Basel)] 2022 Jan 20; Vol. 10 (2). Date of Electronic Publication: 2022 Jan 20.
DOI:	10.3390/vaccines10020155
Abstrakt:	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.
Databáze:	MEDLINE
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