Molecular characterisation and vaccine efficacy of two novel developmentally regulated surface tegument proteins of Fasciola hepatica

McCusker, Paul, Toet, Hayley, Rathinasamy, Vignesh, Young, Neil, Beddoe, Travis, Anderson, Glenn, Dempster, Robert, McVeigh, Paul, McCammick, Erin, Wells, Duncan, Mousley, Angela, Marks, Nikki J., Maule, Aaron G., and Spithill, Terry W. (2020) Molecular characterisation and vaccine efficacy of two novel developmentally regulated surface tegument proteins of Fasciola hepatica. Veterinary Parasitology, 286. 109244.

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Abstract

The surface tegument of Fasciola hepatica is a crucial tissue due to its key role at the host-parasite interface. We characterised three novel proteins, termed Fhteg1, Fhteg5 and Fhteg8, that are found in the tegument membrane fraction of adult F. hepatica. Bioinformatic analysis of proteomic datasets identified Fhteg5 and Fhteg8 as tegumental glycoproteins and revealed that Fhteg1, Fhteg5 and Fhteg8 are associated with exosomes of adult F. hepatica. Fhteg1, Fhteg5 and Fhteg8 appear to be related to uncharacterised sequences in F. gigantica, Fasciolopsis buski, Echinostoma caproni, Clonorchis sinensis, Opisthorchis viverrini, Schistosoma japonicum and S. mansoni, although F. hepatica appears to have expanded this family. Fhteg1 and Fhteg5 were characterised in detail. The Fhteg1 and Fhteg5 gene transcripts each demonstrate significant upregulation in juvenile fluke 2–4 days post-excystment, with transcript levels maintained during development over 3 weeks in vitro. RNAseq data showed that both Fhtegs are expressed in the adult life stage, although the transcript levels were about 8 fold lower than those in juveniles (3 week post infection). Using immunocytochemistry, Fhteg1 and Fhteg5 were each shown to be expressed in cells adjacent to the muscle layer as well as on the surface of 1 week old juveniles, whilst Fhteg5 was also present in cells at the base of the pharynx. RNAi mediated knockdown of Fhteg1 and Fhteg5 transcripts in 4–10 day old juveniles had no effect on parasite survival, movement or growth in vitro. Although no IgG responses were observed for Fhteg1 or Fhteg5 during infection in sheep and cattle, both proteins elicited a low IgG response in a proportion of infected rats. Rats vaccinated with Fhteg1 and Fhteg5 showed good IgG responses to both proteins and a mean 48.2 % reduction in worm burden following parasite challenge. Although vaccination of cattle with both proteins induced a range of IgG responses, no protection was observed against parasite challenge. This is the first study to provide insights into the molecular properties of two novel, developmentally regulated surface tegument proteins in F. hepatica.

Item ID: 75230
Item Type: Article (Research - C1)
ISSN: 1873-2550
Keywords: Cattle, Exosome, Fasciola hepatica, Juvenile fluke, qPCR, Rat, RNAi, Tegument membrane proteins, Vaccine
Copyright Information: © 2020 Elsevier B.V. All rights reserved
Date Deposited: 14 Jul 2022 03:00
FoR Codes: 30 AGRICULTURAL, VETERINARY AND FOOD SCIENCES > 3009 Veterinary sciences > 300909 Veterinary parasitology @ 60%
30 AGRICULTURAL, VETERINARY AND FOOD SCIENCES > 3003 Animal production > 300304 Animal protection (incl. pests and pathogens) @ 40%
SEO Codes: 10 ANIMAL PRODUCTION AND ANIMAL PRIMARY PRODUCTS > 1004 Livestock raising > 100401 Beef cattle @ 30%
10 ANIMAL PRODUCTION AND ANIMAL PRIMARY PRODUCTS > 1001 Environmentally sustainable animal production > 100199 Environmentally sustainable animal production not elsewhere classified @ 40%
10 ANIMAL PRODUCTION AND ANIMAL PRIMARY PRODUCTS > 1004 Livestock raising > 100402 Dairy cattle @ 30%
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