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

Cwiklinski, Krystyna ORCID: 0000-0001-5577-2735, Drysdale, Orla, López Corrales, Jesús ORCID: 0000-0003-2996-7904, Corripio-Miyar, Yolanda ORCID: 0000-0002-1344-7405, De Marco Verissimo, Carolina, Jewhurst, Heather ORCID: 0000-0003-4630-7027, Smith, David ORCID: 0000-0002-5158-0522, Lalor, Richard ORCID: 0000-0003-0433-9805, McNeilly, Tom N ORCID: 0000-0001-6469-0512 and Dalton, John P ORCID: 0000-0003-3829-9186 (2022) Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth Fasciola hepatica. Vaccines, 10 (2). 155-.

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Official URL: http://dx.doi.org/10.3390/vaccines10020155

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.

Item Type:	Article
Uncontrolled Keywords:	Fasciola hepatica, Kunitz-type inhibitor, protease-anti-protease balance, sheep, stefin, vaccines
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	02 Feb 2022 15:46
Last Modified:	14 Mar 2024 17:46
DOI:	10.3390/vaccines10020155
Open Access URL:	https://www.mdpi.com/2076-393X/10/2/155
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3148040