Novel vaccines to combat significant endemic diseases of livestock in Scotland: Gastrointestinal nematode parasites of ruminants
Project Lead
Challenges
Sustainability and food security are two key challenges for the UK agricultural sector. In a changing climate, there is a need to reduce the impact of endemic diseases on livestock health, welfare, and productivity. The brown stomach worm, Teladorsagia circumcincta, is the most prevalent livestock roundworm parasite in the UK and has a major economic impact on the sheep industry. This is due to production losses attributed to reduced live-weight gain and costs associated with treating the problem. The losses cost around £84 million every year (2005 figures). This is equivalent to £4.40 extra per lamb to achieve finishing weight. For the same reasons, the nematode species Ostertagia ostertagi, poses a problem in cattle production.
Current roundworm control relies heavily upon a handful of broad-spectrum compounds (anthelmintics). Unfortunately, roundworms are developing resistance to these to these treatments which allow them to survive.
Other key drivers for this research are:
- The limitations of the current chemotherapeutics
- Reduced efficacy and anthelmintic resistance
- The effects of residues on the environment, operator and food safety
The development of synthetic vaccines might help in mitigating the effects of nematode infection that could be used in conjunction with athelmintics. The initial step for vaccine development is the procurement of host antibodies, produced by either exposing sheep to continuous infection with the sheep-parasitic nematodes, or by vaccination of cattle with complex protein mixtures that induce protection against cattle-parasitic nematodes. These antibodies are then used as the basis for the identification of individual proteins from the nematodes, which can then be incorporated in the vaccines.
Questions
- What economically and biologically viable novel vaccines could be developed to combat significant endemic diseases in Scotland?
Solutions
This project aims to develop highly effective, optimised, safe, novel vaccines for the control of the most production- and welfare-limiting endemic diseases of Scottish livestock caused by parasitic gastrointestinal nematodes (GIN). The critical next step to increase vaccine economic viability and efficacy is to develop vaccine delivery methods which target the most appropriate immune response. We are producing smart-targeted vaccine delivery systems which are more stable and efficacious delivery of treatments to animals, which promotes bioavailability and reactivity.
Development of a multi-species vaccine to control the major gastrointestinal nematodes (GIN) of sheep in temperate regions
We have previously developed a novel prototype recombinant vaccine against one of the most common and important parasitic GIN of sheep, Teladorsagia circumcincta. This prototype offers good levels of protection in lambs and is effective in periparturient ewes. However, it can only target a single species of GIN. Adequate worm control requires a vaccine that can target multiple species if it is to complement anthelmintic treatments. We are addressing this issue by identifying common protective antigens and/or peptide epitopes from T. circumcincta, N. battus and Trichostrongylus spp. We are assessing the efficacy of these “multivalent” vaccines delivered in a range of ways to stimulate the appropriate immune responses.
Development of an economically viable vaccine to control Ostertagia ostertagi in cattle
GIN also represent a major production limitation in cattle. Previously, we have shown that calves were protected when immunised with vaccines based on adult O. ostertagi excretory-secretory products, even at low doses. However, these vaccines are expensive to produce. We are using similar technologies to identify antigens and peptides that can be incorporated into more cost-effective vaccine formulations for testing.
Project Partners
Progress
We have obtained the necessary permissions from the animal health and welfare review body (AWERB) for the work to commence. Lambs have been infected with 2 species of sheep-parasitic nematode (1 species per group of lambs) at regular intervals to induce immunity. Once immunity was established, antibody levels were boosted by a single, final, large infection before serum (the water-like subunit of blood that contains antibodies) was harvested from the lambs. Antibodies from cattle which had been vaccinated with a complex, protective mixture of cattle-parasitic nematode proteins were retrieved from the archives. At this point the reagents needed for identifying good vaccine targets in the nematode species had been acquired whereafter the next phase of the project could be initiated.
For the sheep nematodes this involved developing databases of the proteins which are present in the parasitic stages of the worms, by sequencing the genes switched on in those stages. We did this by extracting the relevant genetic material (RNA) from worms of each stage for both nematode species and sent the samples for sequencing to a company. The results will inform identification of potential vaccine proteins for Year 2. For the cattle-parasitic nematode vaccine development, the more than 450 components of the protective protein mixture have been identified by proteomic analysis. To help in identifying vaccine candidate proteins, any proteins that are predicted to be secreted by the parasitic stages of the nematodes have been identified through computational analysis. These proteins are made of chains of individual amino acids, termed peptides. All of the short peptides (14 to 15 amino acids in length) identified during the computational analysis were arrayed on glass slides and incubated with sera from cattle immunised with the protective protein mixture, to identify the peptides which are the most immunogenic. The capacity of the selected peptides to protect cattle when used in a vaccine will be tested in future years of the project.
Knowledge exchange: The group has provided advice to members of the Scottish Government Animal Health and Welfare Division, Disease Prevention Team, on key diseases for vaccination/control and diagnosis in different settings for incorporation into the new farm payments scheme. We have also been successful in establishing a multi-institutional collaborative project to develop a sheep parasite vaccine, with the University of New England (Australia), the University of Glasgow and colleagues at the James Hutton Institute. Direct interaction with industry stakeholders, involved a Vaccine Highlight event at the Royal Highland Show as well as hosting the Livestock Helminth Research Alliance meeting as well as visits and meetings with commercial partners (e.g., Bimeda, Boehringer Ingelheim, Elanco and Zoetis) that are interested in developing novel anti-parasite vaccines. The group has entered into a partnership with the company PEPperPRINT to exploit their vaccine candidate identification technologies. We have also contributed towards discussion with professional audiences by publishing three papers on livestock vaccines in open access scientific journals, including one in The Lancet Planetary Health (Impact Factor 19.2) and the remaining two in the International Journal of Molecular Sciences and Veterinary Parasitology. We also presented invited talks at meetings held by The Microbiological Society and The University of Glasgow. Public engagement activities included discussions and presentations at the Biggar Science festival and the Royal Highland Show.
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The aim of this RD is to develop safe, highly effective, optimised, novel vaccines for the control of the most production- and welfare-limiting endemic diseases of Scottish livestock. The key drivers for this research are:
- Prevention is better than cure. Anthelmintics (chemotherapeutics for the control of intestinal worms) and antibiotics are used to treat diseases but can leave...
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