A novel ex vivo immunoproteomic approach characterising Fasciola hepatica tegumental antigens identified using immune antibody from resistant sheep

Cameron, Timothy C.; Cooke, Ira; Faou, Pierre; Toet, Hayley; Piedrafita, David; Young, Neil D.; Rathinasamy, Vignesh; Beddoe, Travis; Anderson, Glenn R.; Dempster, R.P.; Spithill, Terry W.

doi:10.1016/j.ijpara.2017.02.004

Cited by 20 publications

(17 citation statements)

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“…Thin Tailed sheep (Cameron et al, 2017). This study identified several molecules consistent with previous analyses of the tegument (Wilson et al, 2011;Hacariz et al, 2012), as well as a range of proteins associated with F. hepatica exosomes (15K EVs; Cwiklinski et al, 2015b).…”

Section: Proteomicssupporting

confidence: 87%

Advances in Fasciola hepatica research using ‘omics’ technologies

Cwiklinski

Dalton

2018

International Journal for Parasitology

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The liver fluke Fasciola hepatica is an economically important pathogen of livestock worldwide, as well as being an important neglected zoonosis. Parasite control is reliant on the use of drugs, particularly triclabendazole, which is effective against multiple parasite stages. However, the spread of parasites resistant to triclabendazole has intensified the pursuit for novel control strategies. Emerging 'omics' technologies are helping advance our understanding of liver fluke biology, specifically the molecules that act at the host-parasite interface and are central to infection, virulence and long-term survival within the definitive host. This review discusses the technological sequencing advances that have facilitated the unbiased analysis of liver fluke biology, resulting in an extensive range of 'omics' datasets. In addition, we highlight the 'omics' studies of host responses to F. hepatica infection that, when combined with the parasite datasets, provide the opportunity for integrated analyses of host-parasite interactions. These extensive datasets will form the foundation for future in-depth analysis of F. hepatica biology and development, and the search for new drug or vaccine interventions.

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Section: Proteomicssupporting

confidence: 87%

Advances in Fasciola hepatica research using ‘omics’ technologies

Cwiklinski

Dalton

2018

International Journal for Parasitology

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“…As such, future vaccine discovery may need to specifically target fasciolid molecules such as surface tegumental proteins/glycoproteins and secreted components, including surface molecules of secreted extracellular vesicles that are involved in early stage migration in the host, in tissue penetration and in immunomodulation [ 5 , 20 , 21 ]. Moreover, the identification of antigens shared between F. hepatica and F. gigantica can provide an avenue for possible development of a dual purpose and cost-friendly vaccine against both liver fluke species [ 22 ]. The availability of substantial data on the transcriptomes of liver fluke species can aid in this process as well as in the identification of new vaccine targets [ 23 , 24 , 25 , 26 , 27 ].…”

Section: Fasciolosismentioning

confidence: 99%

Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines

McManus

2020

Vaccines

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Liver flukes (Fasciola spp., Opisthorchis spp., Clonorchis sinensis) and blood flukes (Schistosoma spp.) are parasitic helminths causing neglected tropical diseases that result in substantial morbidity afflicting millions globally. Affecting the world’s poorest people, fasciolosis, opisthorchiasis, clonorchiasis and schistosomiasis cause severe disability; hinder growth, productivity and cognitive development; and can end in death. Children are often disproportionately affected. F. hepatica and F. gigantica are also the most important trematode flukes parasitising ruminants and cause substantial economic losses annually. Mass drug administration (MDA) programs for the control of these liver and blood fluke infections are in place in a number of countries but treatment coverage is often low, re-infection rates are high and drug compliance and effectiveness can vary. Furthermore, the spectre of drug resistance is ever-present, so MDA is not effective or sustainable long term. Vaccination would provide an invaluable tool to achieve lasting control leading to elimination. This review summarises the status currently of vaccine development, identifies some of the major scientific targets for progression and briefly discusses future innovations that may provide effective protective immunity against these helminth parasites and the diseases they cause.

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“…While the excretory-secretory (ES) products of F. hepatica have been thoroughly investigated as vaccine antigens with little sustained success, the tegument surface represents the key interface in host-parasite interactions, performing numerous functions for the parasite such as nutrient absorption, sensory input and protection from the host immune response (Halton, 2004). Host antibodies have been demonstrated to have an ability to bind to the tegument antigens of F. hepatica (Howell & Sandeman, 1979;Hanna, 1980;Sulaiman et al, 2016;Cameron et al, 2017), suggesting that tegument-directed vaccine candidates warrant further investigation. Despite this, there are few reported cases of tegument-directed vaccines.…”

Section: Introductionmentioning

confidence: 99%

“…is a dynamic syncytial layer surrounded by a glycocalyx (Hanna, 1980;Lammas & Duffus, 1983). Various groups in recent times have attempted to characterize the proteome (Hacariz, Sayers & Baykal, 2012;Ravida et al, 2016;Wilson et al, 2011) and immunoproteome (Cameron et al, 2017) of F. hepatica using mass spectrometry. The proteome of an enriched tegument extract of F. hepatica revealed a range of proteins shared with the schistosome tegument including annexins, tetraspanins, carbonic anhydrase and an orthologue of a host protein (CD59) (Wilson et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

“…A second study enriched tegument glycoproteins using immobilized lectin chromatography to identify over 369 glycoproteins with a broad range of functions such as proteases, protease inhibitors, paramyosin, venom allergen-like protein II and enolase (Ravida et al, 2016). There is an over-abundance of vaccine antigen candidates from the tegument and to narrow down potential candidates, a recent study used a novel ex vivo immunoproteomic technique whereby contact with purified host IgG from infected animals, the flukes will slough (i.e., sheds) its tegument proteins after antibody binding has occurred (Cameron et al, 2017). This immunosloughate identified 38 proteins that could be potential vaccine antigens, (Cameron et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

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Characterization of a profilin-like protein from Fasciola hepatica

Wilkie

Cameron

Beddoe

2020

PeerJ

Self Cite

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Fasciola hepatica is the causative agent of fasciolosis, an important disease of humans and livestock around the world. There is an urgent requirement for novel treatments for F. hepatica due to increasing reports of drug resistance appearing around the world. The outer body covering of F. hepatica is referred to as the tegument membrane which is of crucial importance for the modulation of the host response and parasite survival; therefore, tegument proteins may represent novel drug or vaccine targets. Previous studies have identified a profilin-like protein in the tegument of F. hepatica. Profilin is a regulatory component of the actin cytoskeleton in all eukaryotic cells, and in some protozoan parasites, profilin has been shown to drive a potent IL-12 response. This study characterized the identified profilin form F. hepatica (termed FhProfilin) for the first time. Recombinant expression of FhProfilin resulted in a protein approximately 14 kDa in size which was determined to be dimeric like other profilins isolated from a range of eukaryotic organisms. FhProfilin was shown to bind poly-L-proline (pLp) and sequester actin monomers which is characteristic of the profilin family; however, there was no binding of FhProfilin to phosphatidylinositol lipids. Despite FhProfilin being a component of the tegument, it was shown not to generate an immune response in experimentally infected sheep or cattle.

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A novel ex vivo immunoproteomic approach characterising Fasciola hepatica tegumental antigens identified using immune antibody from resistant sheep

Cited by 20 publications

References 77 publications

Advances in Fasciola hepatica research using ‘omics’ technologies

Advances in Fasciola hepatica research using ‘omics’ technologies

Recent Progress in the Development of Liver Fluke and Blood Fluke Vaccines

Characterization of a profilin-like protein from Fasciola hepatica

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