The rational simplification of a recombinant cocktail vaccine to control the parasitic nematode Teladorsagia circumcincta

Nisbet, Alasdair J.; McNeilly, Tom N.; Price, Daniel D.; Oliver, E. Margaret; Bartley, Yvonne; Mitchell, Mairi C.; Palarea‐Albaladejo, Javier; Matthews, Jacqueline B.

doi:10.1016/j.ijpara.2018.10.006

Cited by 30 publications

(41 citation statements)

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“…Each group (group 1-3) was housed in a separate pen. In alignment with 3Rs principles, lambs in groups 1 and 2 were derived from a vaccine efficacy study recently published by [23] and correspond to the animals described in the synonymous groups enrolled in Trial 6 of said study. Briefly, lambs in group 1 ('Vac/Tc+')) were injected three times with a recombinant vaccine against T. circumcincta, leaving a three-week interval between successive injections; protocols of vaccine production and administration had been described previously [21].…”

Section: Methodsmentioning

confidence: 99%

“…At the end of the trial, worms were enumerated from the abomasa of each sheep using standard techniques [25]. A generalised additive mixed modelling (GAMM) approach was undertaken for analysis of longitudinal FEC data, whilst cumulative FEC values for each sheep (cFEC) were calculated using the trapezoidal method, as described in [23]. Worm burden data were analysed using negative binomial generalised linear models with a logarithmic link function accounting for data over-dispersion as described previously [21][22][23].…”

Section: Parasitological Analyses and Sample Collection For Microbiommentioning

confidence: 99%

“…T. circumcincta resistance to anthelmintics is widespread [19][20], thus making control of this parasite in flocks highly challenging. Recent efforts by Nisbet and colleagues [21][22][23] have resulted in the development of an effective sub-unit vaccine against T. circumcincta, composed of a cocktail of 8 recombinant proteins [21][22][23]. Administration of this vaccine to 6-7 months old lambs resulted in up to 70% and 75% reduction in total worm and faecal egg counts (FEC) (the latter a proxy of parasite burden), respectively, compared to challenged controls, thus representing a promising alternative to the administration of anthelmintics [21].…”

Section: Introductionmentioning

confidence: 99%

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Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

Cortés

Wills

et al. 2019

Preprint

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Background The multifaceted interactions between gastrointestinal (GI) helminth parasites, vertebrate host gut microbiota and the immune system are emerging as a key area of research within the field of host-parasite relationships. In spite of the plethora of data available on the impact that GI helminths exert on the composition of the gut microflora, whether alterations of microbial profiles are caused by direct parasite-bacteria interactions or, indirectly, by alterations of the GI environment (e.g. mucosal immunity), remains to be determined. Furthermore, no data is thus far available on the downstream roles that qualitative and quantitative changes in gut microbial composition play in the overall pathophysiology of parasite infection and disease. Results In this study, we investigated the fluctuations in microbiota composition and local immune microenvironment of sheep vaccinated against, and experimentally infected with, the ‘brown stomach worm’ Teladorsagia circumcincta, a parasite of worldwide socio-economic significance. We compared gut microbial profiles with those obtained from groups of unvaccinated/infected and unvaccinated/uninfected animals. We show that alterations to the gut microbial composition are associated mainly with parasite infection, and that this involves the expansion of populations of bacteria with known pro-inflammatory roles that may contribute to the immunopathology of helminth disease. Using novel quantitative approaches for the analysis of confocal microscopy-derived images we also show that gastric tissue infiltration of T cells is driven by parasitic infection rather than anti-helminth vaccination. Conclusions Teladorsagia circumcincta infection leads to an expansion of potentially pro-inflammatory gut microbial species and abomasal T cells. This data paves the way for future experiments aimed at determining the contribution of the gut flora to the pathophysiology of parasitic disease, with the ultimate aim to design and develop novel treatment/control strategies focused on preventing and/or restricting bacterial-mediated inflammation upon infection by gastrointestinal helminths.

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Section: Methodsmentioning

confidence: 99%

Section: Parasitological Analyses and Sample Collection For Microbiommentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

Cortés

Wills

et al. 2019

Preprint

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“…14,15 Work is ongoing to refine the protein cocktail by testing fewer recombinant protein combinations in vaccine trials. 16 Further, its protective capacity will be tested in newly weaned lambs and in field trials.…”

Section: Teladorsagia Circumcinctamentioning

confidence: 99%

“…41 Vaccines containing multiple antigens of a single parasite species could slow down adaptation of the parasites to the vaccine, such as an experimental Teladorsagia vaccine in sheep that comprises multiple recombinant proteins. 14,16 The effect of the level and duration of vaccine efficacy on parasite transmission and animal productivity and the combined use of vaccines and other control methods in different management systems and climate regions should be simulated using mathematical models to inform vaccine developers and regulatory authorities about possible outcome scenarios.…”

Section: Future Prospects and Summarymentioning

confidence: 99%

Helminth Vaccines in Ruminants

Claerebout

Geldhof

2020

Veterinary Clinics of North America: Food Animal Practice

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KEYWORDS Gastrointestinal nematodes Lungworm Liver fluke Vaccines KEY POINTSOnly a few vaccines against parasitic helminths of livestock are currently on the market; namely those against Dictyocaulus viviparus in cattle, Haemonchus contortus in sheep, and the tapeworm Echinococcus granulosus in sheep.Research is ongoing to develop vaccines based on purified or recombinantly expressed worm proteins for Ostertagia ostertagi and Cooperia oncophora in cattle, for Teladorsagia circumcincta and H contortus in sheep, and for Fasciola hepatica in ruminants. Recombinant expression of worm antigens with the correct conformation to induce protective immunity is still a major challenge in vaccine development. Vaccination is likely to be part of integrated worm control, together with other control measures, such as anthelmintic treatments, biological control, and grazing management. Interdisciplinary research, including social sciences, should investigate drivers of farmers' and veterinarians' decision making, to optimize uptake of vaccination by the end users.Vet Clin Food Anim 36 (2020) 159-171

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Guide to advances in the control of gastrointestinal roundworms in sheep

Crilly¹

2023

In Practice

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Background: In the UK, diseases caused by gastrointestinal nematodes (GINs) are the most expensive endemic diseases, being a major cause of morbidity, mortality and lost production in sheep flocks. Control is complicated by the increasing prevalence of anthelmintic resistance in the GIN population and changes in epidemiology, partially driven by climate change. Therefore, there is great emphasis among sheep farmers and veterinarians to find methods to successfully control GINs and prevent associated diseases. Aim of the article: This article outlines the different strategies that can be implemented on farm to try and sustainably control parasitic gastrointestinal nematodes of sheep.

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The rational simplification of a recombinant cocktail vaccine to control the parasitic nematode Teladorsagia circumcincta

Abstract: Graphical abstract

Cited by 30 publications

References 24 publications

Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

Infection with the sheep gastrointestinal nematode Teladorsagia circumcincta increases luminal pathobionts

Helminth Vaccines in Ruminants

Guide to advances in the control of gastrointestinal roundworms in sheep

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