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

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. View Full-Text

Keywords: Fasciola hepatica; sheep; vaccines; protease-anti-protease balance; stefin; Kunitz-type inhibitor

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Cwiklinski, K.; Drysdale, O.; López Corrales, J.; Corripio-Miyar, Y.; De Marco Verissimo, C.; Jewhurst, H.; Smith, D.; Lalor, R.; McNeilly, T.N.; Dalton, J.P. Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth Fasciola hepatica. Vaccines 2022, 10, 155. https://doi.org/10.3390/vaccines10020155

AMA Style

Cwiklinski K, Drysdale O, López Corrales J, Corripio-Miyar Y, De Marco Verissimo C, Jewhurst H, Smith D, Lalor R, McNeilly TN, Dalton JP. Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth Fasciola hepatica. Vaccines. 2022; 10(2):155. https://doi.org/10.3390/vaccines10020155

Chicago/Turabian Style

Cwiklinski, Krystyna, Orla Drysdale, Jesús López Corrales, Yolanda Corripio-Miyar, Carolina De Marco Verissimo, Heather Jewhurst, David Smith, Richard Lalor, Tom N. McNeilly, and John P. Dalton. 2022. "Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth Fasciola hepatica" Vaccines 10, no. 2: 155. https://doi.org/10.3390/vaccines10020155

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

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