Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth <i>Fasciola hepatica</i>
The liver fluke <i>Fasciola hepatica</i> is an economically important global pathogen of humans and their livestock. To facilitate host invasion and migration, <i>F. hepatica</i> secretes an abundance of cathepsin peptidases but prevents excessive damage to both parasite and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/10/2/155 |
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| author | Krystyna Cwiklinski Orla Drysdale Jesús López Corrales Yolanda Corripio-Miyar Carolina De Marco Verissimo Heather Jewhurst David Smith Richard Lalor Tom N. McNeilly John P. Dalton |
| author_facet | Krystyna Cwiklinski Orla Drysdale Jesús López Corrales Yolanda Corripio-Miyar Carolina De Marco Verissimo Heather Jewhurst David Smith Richard Lalor Tom N. McNeilly John P. Dalton |
| author_sort | Krystyna Cwiklinski |
| collection | DOAJ |
| description | The liver fluke <i>Fasciola hepatica</i> is an economically important global pathogen of humans and their livestock. To facilitate host invasion and migration, <i>F. hepatica</i> 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 (<i>p</i> < 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 <i>F. hepatica</i> peptidase inhibitors were positive indicators for increased weight gain and levels of haemoglobin within the normal range at 16 weeks post-infection (wpi; <i>p</i> < 0.05). These studies point to the potential of targeting peptidase inhibitors as vaccine cocktails for fasciolosis control in sheep. |
| first_indexed | 2024-03-09T20:54:17Z |
| format | Article |
| id | doaj.art-3371f8ffa1b94ba784a90fbdeafd0833 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-03-09T20:54:17Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-3371f8ffa1b94ba784a90fbdeafd08332023-11-23T22:24:25ZengMDPI AGVaccines2076-393X2022-01-0110215510.3390/vaccines10020155Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth <i>Fasciola hepatica</i>Krystyna Cwiklinski0Orla Drysdale1Jesús López Corrales2Yolanda Corripio-Miyar3Carolina De Marco Verissimo4Heather Jewhurst5David Smith6Richard Lalor7Tom N. McNeilly8John P. Dalton9Molecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, IrelandSchool of Biological Sciences, Medical Biology Centre, Queen’s University Belfast, Belfast BT9 5DL, UKMolecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, IrelandMoredun Research Institute, Pentland Science Park, Penicuik, Midlothian EH26 0PZ, UKMolecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, IrelandMolecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, IrelandSchool of Biological Sciences, Medical Biology Centre, Queen’s University Belfast, Belfast BT9 5DL, UKMolecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, IrelandMoredun Research Institute, Pentland Science Park, Penicuik, Midlothian EH26 0PZ, UKMolecular Parasitology Laboratory, Centre for One Health, Ryan Institute, National University of Ireland Galway, H91 DK59 Galway, IrelandThe liver fluke <i>Fasciola hepatica</i> is an economically important global pathogen of humans and their livestock. To facilitate host invasion and migration, <i>F. hepatica</i> 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 (<i>p</i> < 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 <i>F. hepatica</i> peptidase inhibitors were positive indicators for increased weight gain and levels of haemoglobin within the normal range at 16 weeks post-infection (wpi; <i>p</i> < 0.05). These studies point to the potential of targeting peptidase inhibitors as vaccine cocktails for fasciolosis control in sheep.https://www.mdpi.com/2076-393X/10/2/155<i>Fasciola hepatica</i>sheepvaccinesprotease-anti-protease balancestefinKunitz-type inhibitor |
| spellingShingle | Krystyna Cwiklinski Orla Drysdale Jesús López Corrales Yolanda Corripio-Miyar Carolina De Marco Verissimo Heather Jewhurst David Smith Richard Lalor Tom N. McNeilly John P. Dalton Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth <i>Fasciola hepatica</i> Vaccines <i>Fasciola hepatica</i> sheep vaccines protease-anti-protease balance stefin Kunitz-type inhibitor |
| title | Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth <i>Fasciola hepatica</i> |
| title_full | Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth <i>Fasciola hepatica</i> |
| title_fullStr | Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth <i>Fasciola hepatica</i> |
| title_full_unstemmed | Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth <i>Fasciola hepatica</i> |
| title_short | Targeting Secreted Protease/Anti-Protease Balance as a Vaccine Strategy against the Helminth <i>Fasciola hepatica</i> |
| title_sort | targeting secreted protease anti protease balance as a vaccine strategy against the helminth i fasciola hepatica i |
| topic | <i>Fasciola hepatica</i> sheep vaccines protease-anti-protease balance stefin Kunitz-type inhibitor |
| url | https://www.mdpi.com/2076-393X/10/2/155 |
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