Dissecting variation in host responsiveness to a recombinant vaccine designed to control teladorsagiosis in sheep

Lead Research Organisation: Moredun Research Institute
Department Name: Disease Control

Abstract

Delivering food security globally requires that a sustainable, safe and secure supply of quality food be provided by making the most efficient use of inputs. Infectious diseases substantially affect the efficiency of livestock production and parasitic roundworms are major culprits in this arena. Indeed, worm infections are the most costly endemic disease affecting sheep in the UK, with Teladorsagia circumcincta being the dominant worm present in this country. Estimated costs of roundworm infections to the UK sheep industry run at around £80 million per annum.

Dewormers (known as anthelmintics) have been used for over four decades to control worm infections in sheep throughout the world, but resistance to the three traditional drug classes is common. Worryingly, T. circumcincta resistance has already been reported against one of the two new classes of dewormer, even although this product was only launched two years ago. Historically, much resource and research has been directed at selective breeding of sheep for resistance to worms, but there have been few outputs from this work that have made it to practical application on farms in the UK.

An obvious alternative approach to breeding sheep for resistance to worms is to induce resistance to infection in sheep by vaccinating them to specifically stimulate immune protection against worm challenge. This will have the effect of negating the impact of the worms on sheep growth and productivity and importantly, will reduce worm transmission via the environment. Vaccines also hold the advantage over anthelmintic methods of control in that they are not associated with chemical residues in meat, have no environmental impact and are likely to require fewer administration applications over the lifetime of the sheep.

Recently, this research group have had singular success in the discovery of an effective recombinant (sub-unit) vaccine for control of T. circumcincta. This vaccine (known as 'CircVax') comprises 8 recombinant (synthetic) proteins and induces significant, albeit variable, levels of immunity against worm challenge in lambs. The next step in development of this vaccine is to understand the underlying local immune mechanism(s) involved in this variation in sheep responsiveness to the vaccine and to examine if this is affected by the age of the animal. Such a comprehensive understanding of variation in individual responses during vaccination and subsequent worm challenge is essential to optimize the vaccine further (for example, in adjuvant selection) as a tool for integrated worm control in sheep flocks.

The knowledge gained in this project will help determine if the effect of the vaccine can be improved in very young lambs and if responses in older animals can be optimised further. Each of these parameters could be addressed by using more appropriate adjuvants or delivery systems. In addition, if the results point to an inherent inability of the immune system of the very young lamb to control T. circumcincta, the derived information can be exploited in the deployment of the vaccine in a holistic, integrated control strategy that addresses the minimization of selection pressure for drug resistance in the worm.

In summary, the outputs will provide significant steps to developing a commercially relevant vaccine for use by farmers to mitigate the effects of this important parasitic infection of sheep and, as such, fall squarely within the priorities of the BBSRC Animal Health Research Club.

Technical Summary

The overall objective is to understand and overcome variation in host immune responsiveness to a promising Teladorsagia circumcincta sub-unit vaccine prototype, CircVax.

Here, the applicants will analyse parasitological outputs from vaccinated, then challenged, lambs and assess temporal parameters in vaccine responsiveness using recent technological advances in transcriptomics (RNAseq, nextSeq 500 Sequencing) and ovine genomic and immunological tools (http://www.sheephapmap.org/news/OARv2p0.php, http://www.immunologicaltoolbox.co.uk). Using multivariate (general linear mixed models) and network analyses (BioLayoutExpress 3D, Qiagen's Ingenuity Pathway Analysis) to assess relationships between immune gene expression and phenotypic characteristics, and between parasitological outcomes and immune variables and, importantly, how these are affected by lamb age, the project will generate a deep understanding of how sheep respond optimally to CircVax vaccination.

The resultant data will be exploited to develop an understanding of how the vaccine induces immunity against worm challenge and to identify what pathways are different in animals that are not protected by the vaccine. This knowledge, in turn, will be used to optimise the vaccine's effect in the field through optimal delivery(for exmaple, via adjuvant selection) and/or strategic use (for example, in integrated control programmes exploiting the vaccine with minimal use of effective anthelmintics in sheep of different ages).

Planned Impact

It is estimated that the direct global cost of parasitic worms of livestock is ~£1,200M per annum. There are approximately 101 M sheep and 12 M goats in the EU, with the UK having the largest sheep industry in Europe. In the UK, the brown stomach worm, Teladorsagia circumcincta, is the major contributor to parasitic gastroenteritis, estimated to cost the UK sheep industry >£80M each year. Helminths such as T. circumcincta impact hugely on the welfare and productivity of sheep. They do this by affecting growth rate, fertility, meat quality, and wool/milk production and, in heavy infections, by causing clinical disease. The research in this project will impact upon the effect of these worms by furthering development of a much-needed alternative control option; an anti-nematode vaccine known as CircVax.

Chemotherapeutic approaches have been the cornerstone of sheep nematode control for decades; however, resistance to the traditional three broad-spectrum anthelmintic classes is common in T. circumcincta, with resistance already reported to a member of a new class of anthelmintic, monepantel, which was only launched 2 years ago. For these reasons, alternative control methods are sought for sustainable control in the long term. Control by vaccination is the most obvious alternative, with the added value that vaccines have no environmental impact, do not leave chemical residues in food and are likely to require fewer applications over an animal's lifetime. Over the last 8 years, the applicants have developed, designed and tested a recombinant sub-unit T. circumcincta vaccine. Immunisation with this vaccine had a significant effect on worm burden and egg excretion in parasite-challenged lambs >6 months-old. Here, the applicants aim to develop this prototype vaccine further by investigating variation in sheep responsiveness to the vaccine; particularly how immunological unresponsiveness may be overcome in very young lambs. A comprehensive understanding of such responses during vaccination and subsequent parasite challenge is essential to develop this vaccine as a tool for integrated control that will be taken up on UK sheep farms and beyond. The aims are to establish what elements of the local response correlate best with efficacy amongst vaccinates and how variability in vaccine efficacy is affected by lamb age. This knowledge will determine whether or not vaccine efficacy can be improved in young lambs and whether variability in responsiveness in older animals can be addressed by exploiting appropriate adjuvants or delivery systems. Moreover, if the results point to an inherent, and insurmountable, inability to control T. circumcincta in the very young, the information will be used to deploy the vaccine in older animals as part of an integrated strategy to minimise selection pressure for anthelmintic resistance, in particular aiming to preserve use of the Class IV and V anthelmintics.

The outputs of this project will provide significant steps to developing a commercially-relevant subunit nematode vaccine (the 1st of its kind) for use by farmers to mitigate the effects of this important parasite. In so doing, the outcomes address a priority of the Animal Health Research Club ('Understanding variation in vaccine responsiveness and immune-competence at different developmental stages and its impact on disease outcomes'). Industrial stakeholders will benefit through generation of revenue from vaccine sales, as well as from availability of an option that will help prolong efficacy of the remaining effective anthelmintics. In addition, human health policymakers can exploit the data if defined strategies for delivery against ruminant gastrointestinal nematodes can be shown to improve efficacy. This is because there are many similarities (such as host niche, distribution pattern, primary candidate antigens) between the T. circumcincta vaccine and the subunit vaccine currently under development for control of human hookworm.

Publications

10 25 50
 
Description We are studying underlying causes of variation in immune responsiveness to a sub-unit vaccine being developed to control the common abomasal roundworm, Teladorsagia circumcincta, in sheep. Two vaccine trials (one in 3 month-old lambs and one in 6 month-old lambs) were undertaken to investigation variation in immune responsiveness to vaccination and subsequent challenge associated with age and individuality. A unique dataset was generated; in each trial, half the lambs were fitted with an indwelling abomasal cannula to allow dynamic comparison of critical immune responses generated during the period of parasite challenge after vaccination.
Parasitological results: Both age groups had significantly lower worm burdens at the trial end-point in vaccinated compared to control lambs. There was a significantly lower worm burden in 6 month-old compared to 3 month-old lambs, irrespective of whether lambs received the vaccine or not. The vaccine protected the younger lamb group against disproportionally high worm egg shedding compared to the control challenge group. As predicted, intra-group variation in parasitological parameters was observed in both trials.
Immunological assay results: Antibody analyses showed that serum IgG to the recombinant protein components of the vaccine followed a similar dynamic for each antigen. In 3- and 6 month-old vaccinates, IgG levels increased from first to third vaccination, then declined by the end of the trial after challenge. Serum IgG levels (at Day 43) to some vaccine components (APY-1, ASP-1, MEP-1, TGH-2) showed a significant negative correlation with worm burden in the 6 month-old vaccinates (Spearman correlation). A specific recombinant protein serum IgG response was not seen in adjuvant-only recipients. Serum IgG to L3 native antigen was investigated; IgG levels against this antigen were significantly higher in 6 month-old compared to 3 month-old lambs (Day99, P<0.05, ANOVA with multiple comparisons). An increase in serum IgA against L3 antigen was seen in 6 month-old lambs, which was significantly higher at Day64 than in other groups (P<0.05, ANOVA with multiple comparisons). A small increase in IgA was seen between primary vaccination and Day99 in all groups to L4 and adult antigen, with no significant difference between the groups. No increase in IgE was observed for any antigen in any group. Variation in serum responses between individuals was observed in all groups.
Transcriptome analysis: RNA replicates sampled from all lambs at each time-point were pooled and 304 samples subjected to RNASeq. Due to high dataset dimensionality, principal component analysis, multidimensional scaling (MDS) and t-Distributed Stochastic Neighbour Embedding (t-SNE) were used to reduce the gene-wise dimension and visualise datasets in 3D and 2D, respectively. Transcripts in lymph node and abomasal mucosa samples obtained at necropsy separated from those in abomasal temporal biopsies, suggesting tissue and sampling method generate distinct expression profiles. Further, time-points Week 0 and 1 were distinct from Weeks 2 to 6 post challenge. This coincides with larval presence, then emergence from tissue. For the functional analysis, we performed both classical analysis of differentially expressed (DE) genes and a machine learning-based analysis. For the former, DE genes across weeks between vaccinates and controls, between age groups, and between time points. Older lambs expressed a greater range and higher levels of genes involved in immune responses to helminths, epithelial damage, and bacteria the longer lambs, and these responses were exacerbated by the vaccine. In particular, the vaccine triggered in the older lambs, but not the younger lambs, significant increases in the expression of genes involved in T and B cell, antigen presenting cell, and immune cell activation and recruitment pathways.
We are also interested in the variation in immune gene expression that best predicts immunity to T. circumcincta at the individual level, how these immune pathways change over time, and whether lamb age affects how vaccine-elicited immune pathways change over the course of the 9-week vaccination and infection regime. To address these questions, we developed a bespoke machine learning (ML) pipeline, which has led to three publications so far using different biological systems (Babayan et al. 2018, Sci Rep, Babayan et al. 2018, Front. Immunol., and Babayan et al 2018, Science). After an 11-month hiatus for the maternity leave of our post-doctoral research assistant, this analysis of the sheep transcriptomes is now complete. We show that the immune status of sheep after immunisation, but before challenge with infective L3, is the most predictive of final worm burdens and of total faecal egg output, that there is overlap but also differences between immune pathways that predict worm and egg burdens, older sheep initiate and maintain strong protective immune pathway expression levels throughout the infection period, which younger lambs show gradual increases in immune gene expression even when vaccinated. Importantly, vaccination itself shifts the expression of protective immune pathways earlier in their response to live infection than non-vaccinated animals. The dynamics of these changes appear to differ between arms of the immune system, which "blocks" of pathways associated with epithelial integrity, cell signalling, innate cellular activity, and adaptive immunity following different expression profiles over time. These results are currently being written up for submission to a high impact journal.
Exploitation Route The findings here can be applied to other scientists working on nematode vaccines, because there have been major hurdles to developing these biologicals commercially, one of the main hurdles being the lack of responsiveness in individuals, particularly in young animals. The outputs will help define both antigen and adjuvant selection in this and other host/parasite systems.
In addition, UoG, supported by MRI, are developing novel analytical approaches to analyse longitudinal transcriptome datasets, with a view to identify immune pathways that predict parasite burdens and vaccine efficacy. We will make available our analytical pipeline as part of publications of our results. We also plan to package these software tools for, and make them applicably to, a wider set of biological problems for dissemination to a wider public. This requires substantial effort and specific expertise, and thus is the main focus of a recent UoG-led grant proposal to the BBSRC. If successful, we will disseminate the resulting statistical tools for the analysis of high throughput 'omics data, with the option of including time-structured sampling, as an open-source software package for the benefit of the research community.
Sectors Agriculture, Food and Drink,Digital/Communication/Information Technologies (including Software)

URL https://www.sciencedirect.com/science/article/pii/S0020751919300049
 
Description Data used to help develop Technical Review document for vaccine and also in discussions with regulatory personnel on how a dossier will be developed for approval of the vaccine as a veterinary medicine.
First Year Of Impact 2017
Sector Agriculture, Food and Drink
Impact Types Economic

 
Description Membership of UK Veterinary Products Committee (Matthews, 3 X meetings 2018).
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Ministerial Appointment on Veterinary Products Committee. JB Matthews. Advice on future options for controlling sheep worms, including vaccines and the T circumcincta vaccine specifically
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Participation in Veterinary Products Committee meetings (JB Matthews X 3, 2017).
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description EU H2020
Amount € 8,990,000 (EUR)
Funding ID 635408 
Organisation EU-T0 
Sector Public
Country European Union (EU)
Start 04/2015 
End 03/2019
 
Title Biological samples comprising large archive of material from vaccinated and non-vaccinated sheep. 
Description A resource of unique biological samples archived covering material derived from vaccinated and non vaccinated lambs over the course of vaccination and challenge with nematode larvae. 
Type Of Material Biological samples 
Provided To Others? No  
Impact This large and unique resource is being used in the current project to address specific questions regarding the source of immune variation in the context of protective responses to T circumcincta in vaccinated and nematode challenged only sheep. Archived samples will be available for related, or new, studies by the investigators and collaborators. 
 
Title Longitudinal dataset of tissue-specific RNA-seq transcriptomes and parasite survival and egg production 
Description We have generated an extensive longitudinal RNA-seq dataset of ~14,000 genes measured across 9 weeks of infection in abomasal tissue (5 time points) and lymph nodes (post-mortem), and a matched dataset of longitudinal faecal egg counts and worm burdens taken from the same time points and individual sheep. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact We are currently exploiting this dataset as part of this project. It will be made available in due course after completion of this award. 
 
Description Collaboration on variation in responsiveness to Teladorsagia vaccine: transcriptomics and bioinformatics 
Organisation University of Glasgow
Department Institute of Biodiversity, Animal Health and Comparative Medicine
Country United Kingdom 
Sector Academic/University 
PI Contribution We are supplying information on the vaccine, parasitological, immunological and veterinary expertise. We are supplying RNA material from vaccinated sheep to be analysed for trascriptomic profiles at UoG.
Collaborator Contribution The UoG partners are performing the transcriptomics and downstream bioinformatics analyses.
Impact No outputs yet; new collaboration. Research project ongoing. Disciplines covered - parasitology, immunology, statistics, bioinformatics.
Start Year 2015
 
Title Vaccines. Sheep nematode vaccine. With AJ Nisbet (Moredun), Co-PI. EU (under review), US (granted - US9,717,780B2), Brazil and Uruguay (under review), New Zealand (granted - 629420). 
Description The invention is based upon the identification of a number of antigens derived from species of the genus Teladorsagia, which can be used to raise immune responses in animals-particularly those animals susceptible or predisposed to infection by (or with) one or more Teladorsagia species. The antigens may be exploited to provide compositions and vaccines for raising protective immune responses in animals-the protective immune responses serving to reduce, prevent, treat or eliminate Teladorsagia infections/infestations. 
IP Reference GB201202090 
Protection Patent granted
Year Protection Granted 2017
Licensed Commercial In Confidence
Impact Proof of concept established and confirmed. Vaccine progressing to field trials.
 
Title A sub-unit vaccine for control of teladorsagiosis in sheep 
Description A vaccine prototype for control of teladorsagiosis, which comprises eight recombinant proteins, has been shown to induce significant levels of protection in several independent pen trials in lambs and ewes. The vaccine has been refined to comprise two components. Small scale field trials with this vaccine are underway. Studies to model how the vaccine might be applied and operate under field conditions in the UK are also being completed. Patents are secured, seed stocks and methodologies for upscale have been established and a Target Product Profile completed. 
Type Therapeutic Intervention - Vaccines
Current Stage Of Development Refinement. Non-clinical
Year Development Stage Completed 2019
Development Status Actively seeking support
Impact The major cause of parasitic gastroenteritis (PGE) in small ruminants in temperate regions worldwide is the parasitic nematode, Teladorsagia circumcincta. This pathogen is acquired by ingestion of infective third stage larvae from pasture and, thereafter, the developing parasites and adult worms reside in the abomasum, where a combination of nematode-induced damage and a host inflammatory/immune responses result in a protein-losing gastropathy. The major effect of infection with this parasite is on lamb productivity causing a reduction in live-weight gain; worm infection early in life has a significant impact on lamb body fat and protein deposition as a result of a reduction in the efficiency of metabolisable energy used for growth. The additional cost of lamb finishing time, assuming a 10% reduction in daily weight gain resulting from PGE, is substantial and was recently estimated as £4.40 per lamb. Protective immunity to T. circumcincta develops after exposure to the parasite over a period of weeks; however, the degree of immunity acquired is dependent on the level of parasite challenge, age of the animal and its genotype (Singleton et al., 2011). In practice, immunity usually develops too late to prevent the parasite's negative effects on lamb productivity. T. circumcincta infection is currently controlled using anthelmintics; however, resistance to Class I to III products (benzimidazoles, levamisoles and macrocyclic lactones) is rife and multi-class resistant isolates have been reported. Of further concern are the field reports of resistance to one of the two new classes of anthelmintic. As an alternative method of control, we have developed a recombinant vaccine for T. circumcincta which has been shown to induce significant levels of protective immunity across a range of pen trials in lambs and ewes. Reductions in faecal egg output observed in our studies will have a substantial impact on downstream pasture contamination and could play a central role in the delivery of sustainable integrated nematode control programs on sheep farms across the globe. 
 
Description BBSRC Animal Health Research Club Final Dissemination Event. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presentation of progress on BBSRC-ARC project "Dissecting variation in host responsiveness to a recombinant vaccine designed to control teladorsagiosis in sheep" by Simon Babayan.
Year(s) Of Engagement Activity 2018
 
Description An invited research seminar on development of the vaccine. AgResearch NZ. AJ Nisbet 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Controlling Teladorsagiosis by vaccination, AgResearch, Palmerston North, New Zealand. 5th May 2016
Year(s) Of Engagement Activity 2016
 
Description Australian Society for Parasitology Conference Plenary and Elsevier IJP Award 2017. Sheep nematode vaccine development. JB Matthews 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact International Journal for Parasitology Lecture, Elsevier Series Award, 2017. Conference of the Australian Society for Parasitology. Trials and tribulations of nematode sub-unit vaccine development; a tale from Scotland. Plenary. (New South Wales, Australia, June 2017). JB Matthews provided overview on the vaccine's latest developments including information from this project.
Year(s) Of Engagement Activity 2017
URL http://parasite.org.au/wp-content/uploads/2017/06/ASPnewsletterVol28Vol3-lores-1.pdf
 
Description British Society for Parasitology Meeting. Vaccines Session Plenary. Livestock nematode vaccines: are we there yet? (Dundee, Apr 2017). JB Matthews 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact British Society for Parasitology Spring Meeting. Livestock nematode vaccines: are we there yet? Plenary. (Dundee, Apr 2017). Talk on development of sheep nematode vaccine. Talk included information generated in this project.
Year(s) Of Engagement Activity 2017
URL http://bsp.uk.net/wp-content/uploads/2016/10/bsp-poster-2017-051016new.pdf
 
Description British Veterinary Association London Vet Show. Applying sustainable worm control in sheep. (London, Nov 2017). JB Matthews 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact British Veterinary Association London Vet Show. Applying sustainable worm control in sheep. (London, Nov 2017). This talk covered the issue of anthelmintic resistance in sheep nematodes and how vaccines could be used to in future in integrated control strategies. The talk included information from this project.
Year(s) Of Engagement Activity 2017
 
Description First presentation at BBSRC ARC Dissemination Meeting JB Matthews 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact Matthews (Principal Investigator) gave a presentation on the BBSRC Animal Health Research Club (ARC) project, Dissecting variation in host responsiveness to a recombinant vaccine designed to control teladorsagiosis in sheep, to an audience including other scientists, the ARC Steering Committee, BBSRC representatives and other interested parties from the animal health industry. This talk preceded the start of the project and outlined the background work to the project, focussing on the development of the Teladorsagia circumcincta sub-unit vaccine for the control of a significant roundworm infection of sheep.
Year(s) Of Engagement Activity 2015
 
Description Invited Research Seminar (Liverpool) AJ Nisbet 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact Talk on research progress of the vaccine to other scientists.
Year(s) Of Engagement Activity 2016
 
Description Invited Research Seminar (New Zealand) T McNeilly 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact 17/02/2017: Lincoln University, NZ: Immunity to Teladorsgia circumcincta and implications for control
Year(s) Of Engagement Activity 2017
 
Description Invited presentation to Aquaculture UK meeting - to discuss how work on parasite vaccines (including T circumcincta vaccine) in animals can inform parasite vaccine development for fish. JB Matthews 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Aqua UK Conference. Sustainable parasite control; how do we integrate new vaccines into disease control policies? Lessons for aquaculture. (Aviemore, May 2016). JB Matthews
Year(s) Of Engagement Activity 2016
 
Description Invited presentation to BBSRC ARC Dissemination meeting. Project progress update. JB Matthews 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact BBSRC Animal Health Research Club Dissemination Meeting. Dissecting variation in host immune responsiveness to a recombinant vaccine designed to control teladorsagiosis. (Edinburgh, Nov 2016). JB Matthews
Year(s) Of Engagement Activity 2016
 
Description Invited presentation to EU Veterinary Vaccinology Workshop - parasite vaccines (Including T circumcincta vaccine). JB Matthews 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact EU Veterinary Vaccinology Network Meeting. The challenge of developing multicellular parasite vaccines. (Ghent, May 2016). JB Matthews
Year(s) Of Engagement Activity 2016
URL http://www.vetvaccnet.ac.uk/sites/vetnet/files/user-files/research-paper/pdf/06-16/UK%20VVN%20Meetin...
 
Description Invited research presentation at conference. Development of the vaccine. AJ Nisbet 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Immunobiology in vaccine development against gastrointestinal nematodes of sheep. AJ Nisbet
IAD 2016 - 10th Symposium of the French network for Domestic Animal Immunology, Ploufragan, France, 18th March 2016.
Year(s) Of Engagement Activity 2016
 
Description Invited research presentation at conference. Development of the vaccine. AJ Nisbet 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Controlling Teladorsagiosis by vaccination, AgResearch, Lincoln, New Zealand.
10th May 2016
AJ Nisbet
Year(s) Of Engagement Activity 2016
 
Description Invited talk at the 9th International Sheep Veterinary Congress, Harrogate 22-May-17 to 26-May-17. AJ Nisbet 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Alasdair J. Nisbet, Tom N. McNeilly, Yvonne Bartley, E. Margaret Oliver, Javier Palarea-Albaladejo, Jacqueline B. Matthews. Sustainable production: Protection of sheep against Teladorsagia circumcincta infection by vaccination. 9th International Sheep Veterinary Congress, Harrogate 22-May-17 to 26-May-17. Invited talk to sheep vet surgeons to update them on progress of the vaccine, including information from this project.
Year(s) Of Engagement Activity 2017
 
Description Invited talk on worm vaccines (including progress with T circumcincta vaccine). BBSRC Vet Vaccinology Network. JB Matthews 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact BBSRC UK Veterinary Vaccinology Network Annual Meeting. PARAGONE - an EU H2020 project on parasite vaccines (Manchester, Jan 2016).
JB Matthews
Year(s) Of Engagement Activity 2016
URL http://www.vetvaccnet.ac.uk/news/2016/01/highlights-uk-veterinary-vaccinology-network-conference-201...
 
Description Invited talk to sheep veterinarians on how worm vaccines are being developed. T McNeilly 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact 27/09/16: Sheep Veterinary Society annual meeting, Newquay UK: New ways to tackle the threat of worms: the development of vaccines
Year(s) Of Engagement Activity 2016
 
Description Overview of worm vaccine development to sheep farmers - AJ Nisbet 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Industry/Business
Results and Impact New ways to tackle the threat of worms: vaccines against parasitic nematodes. National Sheep Association, South West Sheep event, Tisbury, Wiltshire. 7th June 2016.
AJ Nisbet
Year(s) Of Engagement Activity 2016
 
Description PARAGONE Consortium Meeting III. Vaccine prototype progress, including progress of the T circumcincta vaccine studied in this project. (Cordoba, Mar 2018). 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact Presented a summary of vaccine progress to the PARAGONE consortium comping 17 partners from academia and the animal health industry from the EU and South America.
Year(s) Of Engagement Activity 2018
URL https://www.paragoneh2020.eu/summary-report-of-paragones-third-principal-consortium-meeting-cordoba-...
 
Description PARAGONE Stakeholder Workshop on Worm Vaccines 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Matthews and Nisbet presented information and led discussions with stakeholders on the options for use of the T circumcincta vaccine - data from this project was presented alongside data from other funded project (EU Horizon 2020 and Scottish Government).
Year(s) Of Engagement Activity 2019
 
Description Presentation on the worm vaccine to trade delegation from Taiwan - AJ Nisbet 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Vaccine Research at Moredun. Presentation to the Taiwanese trade delegation visit, Moredun 9th Sept 2016.
Year(s) Of Engagement Activity 2016
 
Description RCVS Fellowship Day. Dealing with the worms that turned. (Royal Institution, Oct 2018). 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact As part of my fellowship (FRCVS) presentation I discussed the challenges involved in developing vaccines for parasitic nematodes referring to our currently funded work such as this BBSRC project
Year(s) Of Engagement Activity 2018
URL https://www.rcvs.org.uk/news-and-views/news/new-strategy-for-the-fellowship-outlined-at-special-even...
 
Description Second presentation at ARC Dissemination Meeting T McNeilly 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Industry/Business
Results and Impact McNeilly (Co-investigator) gave a presentation on the BBSRC Animal Health Research Club (ARC) project, Dissecting variation in host responsiveness to a recombinant vaccine designed to control teladorsagiosis in sheep, to an audience including other scientists, the ARC Steering Committee, BBSRC representatives and other interested parties from the animal health industry. This talk was an update on progress of the project (talk given at Month 8) and detailed the first year outputs from vaccine trials in two ages of sheep (3- and 6-months-old). The methodology for obtaining serial samples of abomasa material via an in-dwelling cannula was described, along with the faecal worm egg count analysis in vaccinated versus control (non-vaccinated) sheep.
Year(s) Of Engagement Activity 2016
 
Description Sheep Veterinary Society Spring Conference 2018, 21st-23rd May, Aberystwyth Invited speaker: Tom McNeilly 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Tom provided an update on anti-nematode vaccination in sheep
Year(s) Of Engagement Activity 2018
 
Description Soapbox Science Event. My life with worms. (Edinburgh Royal Mile, May 2018). 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Soapbox Science is a novel public outreach platform for promoting women scientists and the science they do. At the Edinburgh 2018 event I talked about developing vaccines for worms citing some of the work in this BBSRC grant.
Year(s) Of Engagement Activity 2018
URL http://soapboxscience.org/soapbox-science-2018-edinburgh/
 
Description Stakeholder presentation on the potential of nematode vaccines for livestock. JB Matthews 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact University of Las Palmas, Gran Canaria, Veterinary Faculty Seminar Series. Vaccines for parasitic nematodes; how these fit into control programmes (Gran Canaria, May 2017). Workshop for veterinarians, politicians, policymakers and farmers of the Canary Islands. Information from this project was included in the presentation.
Year(s) Of Engagement Activity 2017
URL https://www.paragoneh2020.eu/reportaje-workshop-on-inmunological-tools-and-livestock-infection-model...
 
Description Talk on the development of a vaccine to control teladorsagiosis, including a background to the BBSRC ARC project, at International Parasitology Conference (Liverpool) JB Matthews 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact A plenary talk was delivered at the World Association for the Advancement for Veterinary Parasitology Conference on the development of the sub-unit vaccine for the control of teladorsagiosis, including a summary of the research thus far, as well as an introduction to new, associated projects funded by the BBSRC (ARC) and the EU (H2020 Programme). The audience mostly comprised other veterinary parasitologists. It was given in Liverpool in Aug 2015.
Year(s) Of Engagement Activity 2015
 
Description University of Edinburgh CIIE 2018 Summer Retreat. Are sub-unit vaccines for helminths feasible? (Dunkeld, June 2018). 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact A presentation to a summer retreat, hosted by University of Edinburgh's Centre for Infection, Immunology and Evolution, focussed on early career development of scientists working in infection biology
Year(s) Of Engagement Activity 2018
URL http://ciie.bio.ed.ac.uk
 
Description University of Manchester Research Infrastructure Vaccine Network Meeting. Sub-unit parasite vaccines for livestock. (May 2017). JB Matthews 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact University of Manchester Research Infrastructure Vaccine Network Meeting. Sub-unit parasite vaccines for livestock. Invited presentation. (Manchester, May 2017). Presentation to scientists from different disciplines on the challenges of developing vaccines for multicellular parasites. Talk included information from this project.
Year(s) Of Engagement Activity 2017
 
Description Veterinary Products Committee Open Meeting. Anthelmintic resistance and prescribing. (Surrey, Sept 2017). JB Matthews 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Policymakers/politicians
Results and Impact Veterinary Products Committee Open Meeting Seminar. Anthelmintic resistance and prescribing. (Surrey, Sept 2017). This presentation discussed best practice control of livestock and equine helminths. In the discussion afterwards we talked about the concept of vaccinating sheep against nematodes, with the discussion covering proof of concept supported by the research in this project.
Year(s) Of Engagement Activity 2017
URL https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/649775/_1261759-v1-VPC_Ope...