Novel vaccines to combat significant endemic diseases of livestock in Scotland: Vaccine Delivery Platforms

Animal Disease
2022-2027
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Project Lead

Challenges

Infestation of the skin with Psoroptes Ovis (sheep scab mite) represents a major animal welfare and economic burden on the sheep industry. A prototype sheep scab vaccine is effective at controlling sheep scab with an efficacy of over 80% (lesion size reduction). However, the development of a vaccine was considered a ‘market failure.’ The ever-decreasing amount of treatment options means sustainable control approaches are becoming more attractive.

Bovine Respiratory Disease (BRD) in cattle remains a significant problem in the beef and dairy industries. BRD is caused by a variety of infectious agents. Most outbreaks start with viral infection. The key viruses involved in the disease are respiratory syncytial virus (BRSV), parainfluenza 3 virus (PI3V), bovine herpesvirus 1 (BHV-1) and bovine viral diarrhoea virus (BVDV). BRD is still a significant problem despite several vaccines and medications being commercially available. This suggests these options are not sufficiently effective.

BVDV eradication in Scotland has progressed well and is no longer an issue. Vaccines for the other viruses are moderately protective against disease but ineffective in controlling the spread of disease. Modified live vaccines induce broader, more complete immune responses. However, viral proteins have evolved to significantly interfere with the immune response. Further, modified live virus vaccine strains of BHV-1 can appear in vaccinated animals and, when reactivated reduce the immune response. Similar latency and reversion issues appear for virulence bovine respiratory syncytial virus.

In sum, there are several key challenges related to:

  • Overcoming the limitations of the current chemotherapeutics; reduced efficacy and antibiotic resistance; and the effects of residues on the environment, operator, and food safety.
  • Providing increased productivity and efficiency in livestock production with the economic, food security and environmental benefits which accrue from that.

Questions

What economically and biologically viable novel vaccines could be developed to combat significant endemic diseases in Scotland?

Solutions

This project is developing highly effective, optimised, safe, novel vaccines for the control of some of the most production- and welfare-limiting endemic diseases of Scottish livestock.

 

Novel Vaccine for Sheep Scab

To progress the current prototype vaccine towards commercial exploitation, we need to optimise and standardise the delivery methods and dosing regimen. We are assessing a range of vaccine delivery platforms for increased efficacy and longevity. We are modelling to determine the level of protection required for the vaccine to have an impact on the transmission of disease within and between flocks. We are assessing the possibility of reducing the current three doses to a two-dose regime, as well as optimising how to administer it. We are also determining how long the vaccine-induced antibody response is to inform on the need for booster injections.

 

Vaccine Delivery Platforms for Bovine Respiratory Diseases and other livestock pathogens

We are developing novel viral-vectored approaches to produce better vaccines for BRD, specifically targeting the cell-mediated immune response. This involves designing payloads that induce a robust antibody response in the first instance and induce a strong cellular immune response in the second. Delivery of vaccine payloads that induce cellular immunity can be achieved by using viral vectors which produce the recombinant viral protein within the cells. The result is a comprehensive immune response that live attenuated vaccines can induce while limiting the negative effects of live, intact, replicating viruses all without the threat of reversion to virulence inherent to live, attenuated virus vaccines.

Progress

2025 / 2026

Vaccine for sheep scab: A revised efficacy trial for the optimised sheep scab vaccine started in Autumn 2025 and is due to be completed in March 2026. This trial will provide crucial data confirming the degree of protection afforded by the improved sheep scab vaccine under a natural challenge infestation with the sheep scab mite, Psoroptes ovis.

Vaccines for round worms using plant virus vectors: We have successfully attached key T. circumcincta antigens to various tobacco mosaic (TMV) and turnip yellow mosaic (TYMV) virus-like particles (VLPs) using isopeptide/chemical approaches, forming bulk vaccine presentation systems. TMV derived VLPs were shown to be of greater utility than the TYMV as they could be produced in greater amounts and were easier to modify using chemical/isopeptide approaches. Attachment of antigens to TMV VLPs using isopeptide approaches is the favoured option due to the enhanced speed and specificity of antigen attachment over other chemical methods. TMV VLPs and antigens were provided to the in vitro culture systems project to assess immune cell activation in mucosal organoid models. This is a prelude to later vaccination trials in ruminants.

Vaccines for bovine respiratory disease: Our work developing next generation bovine respiratory disease  (BRD) complex vaccines under this RESAS program has allowed us to validate the approach of using virus derived vaccine vectors to deliver vaccine antigens in a manner that induces strong immune responses. The Adenovirus vectors expressing bovine herpesvirus 1 (BoHV1) protein (gpB) have been tested for immunogenicity in cattle. Results show a strong antibody response to the antigens delivered via vaccination using these vaccine vectors. A second vector expressing bovine respiratory syncytial virus (BRSV) protein (gpG) is being tested in vitro for expression.

The lentiviral vector (maedi visna virus) has been used to study delivery of various vaccine antigens in sheep, however, this is the first study to test vaccination of cattle. A study we carried out previously with the lentiviral vector expressing the herpesvirus antigen showed that vaccination with the “sheep dose” resulted in an immune response in cattle but this was less than that generated by adenoviral vectors. New lentiviral vector preparations have been made to conduct a dose titration study in cattle, scheduled for the present quarter (Q4, Y4). This study will provide data for the appropriate dose of this lentiviral vector for cattle vaccination. The wildebeest herpesvirus 1 (AlHV-1) recombinant viruses have also been produced, expressing the same BRSV and BoHV1 proteins. They have now been expanded and are ready for testing. 
 

Impact

Policy.

Vaccine for sheep scab: Sheep scab represents an increasing animal health and welfare issue for the livestock industry in the UK. Control is currently limited to two pharmaceutical treatments, the macrocyclic lactone injectables, where we now have confirmed resistance, and organophosphate plunge dipping, with issues around safe disposal of the dip fluids and minimising environmental harm. The development of a sheep scab vaccine offers real hope for the future sustainable control of the disease and its use is now being incorporated into a future UK-wide control strategy for sheep scab.

Vaccines for bovine respiratory disease (BRD): As the COVID pandemic showed, the use of virus vector technologies, in particular adenovirus vectors, allows for the rapid development of new vaccines. Once efficacy is established, the vaccine can be readily produced for distribution. We have successfully expressed antigens of of critical viral pathogens of BRD three vaccine vectors as potential next generation vaccines. A SPARKS Newsletter describing this was published in Feb.

Industry.

Vaccine for sheep scab: Active discussions continue with our preferred industry partner on the commercialisation of the sheep scab vaccine. The current focus is on how the prototype vaccine can be further simplified and how the expression of the three antigens that form the cocktail vaccine can be scaled up to a level suitable for commercial production.

BRD Vaccines: This research will allow our industrial partner to decide which of these virus derived vaccine vectors delivering BRD antigens are taken forward to commercial development. These vectors are proven to be very safe in multiple species and importantly, there is no need to use adjuvants. Injection site reaction is very rare with these vaccines and when observed is minimal and resolves quickly.

Academia.

Vaccines using plant virus vectors: We have developed new vaccine platforms expressing an array of sheep round worm antigens (T. circumcincta) onto the surface of the plant virus vector , tobacco mosaic virus (TMV) virus-like particles (VLPs). Simply by mixing the surface tagged TMV particles with any prepared antigen leads to their rapid decoration on TMV particle. This will be assessed using the TMV VLPs/T. circumcincta antigen exemplar in further in vitro tests, followed by vaccine trials. We anticipate these vaccines will provide improved and durable protection against economically important intestinal round worm infections in sheep, such as T. circumcincta, while improving livestock health and wellbeing.

Vaccines for BRD. We are expressing antigens of BRD pathogens in three vaccine vectors, adenovirus 5, maedi visna virus, and Alcelaphine herpesvirus-1. This research has been leveraged to secure an Industrial Partner Award from BBSRC with large animal healthcompany to expand these studies testing the same vaccine vectors delivering more antigens

General Public.

Sheep Scab: Further talks have been held with stakeholders, SCOPS, the NSA, and the sheep scab industry working group as to how a future sheep scab vaccine can be used as part of a combined approach (with diagnostic tools and existing drugs) to achieve sustainable control of sheep scab.
 

2024 / 2025

Objective 1: The final efficacy trial for the now optimised sheep scab vaccine is now underway, which will provide crucial data for how the new vaccine formulation and delivery regime performs under a challenge infestation with P. ovis. This will provide important data that can feed into future modelling studies. At the same we have continued discussions with key industry stakeholders and potential commercial partners to define the way in which the vaccine can be used as part of a combined approach (with diagnostic tools and existing drugs) to achieve sustainable control of sheep scab.

Objective 2: We have successfully developed chemical linkage methods to attach existing proteins and peptide antigens to different virus-like particles (VLPs). Components of these are being screened in mucosal organoid models to assess immune cell activation (MRI-A2-1). This technology will be deployed in Year 4 to produce VLPs decorated with discovered/optimized vaccine and adjuvant candidates.

Objective 3: Viral vaccine vectors have been produced that express, in vitro, glycoprotein antigens of the bovine respiratory disease (BRD) viral pathogens, bovine herpesvirus 1 (BHV-1) and bovine respiratory syncytial virus (BRSV). Specifically, the glycoprotein B (gpB) from BHV-1 was expressed in both adenovirus 5 (Ad5) and maedi visna virus (MV) vectirs and subsequently tested for immunogenicity in cattle. Both vaccine vectors elicited a serum antibody response to gpB, but this was of higher titre in the Ad5 vaccinated animals. Ad5 expressing glycoprotein G (gpG) of BRSV has been produced successfully. A cattle trial of this vector has been completed and the serum antibody response is being assessed. Expression of gpG in MV as well as expression of both gpB and gpG in the alcelaphine herpesvirus (AlHV-1) vector are still in process. The planned contingency of using orf virus as an alternative viral vector for these antigens has been initiated. 

2023 / 2024

Sheep scab, worm infections in sheep, and bovine respiratory disease (BRD) in cattle remain major challenges for livestock farmers in Scotland and across the UK. They affect animal welfare, farm productivity, and the economic sustainability of livestock systems. This project is developing new vaccines to help control these diseases, and all milestones for Year 2 have been successfully met.

Sheep scab vaccine: A key trial tested the minimum effective dose of a new sheep scab vaccine. By comparing different antigen concentrations, researchers identified how much of the vaccine payload is needed to produce a strong immune response. These results are shaping the final vaccine design and will be used in discussions with industry partners to bring the vaccine closer to market.

Innovative vaccine platforms: The team has made big strides in improving yields of virus-like particles (VLPs) from plant and bacterial systems. By refining the production and purification process, they are now able to produce higher yields of vaccine particles and attach antigens more efficiently – creating ready-to-use vaccine products more quickly.

Bovine respiratory disease (BRD) vaccines: Using adenovirus vectors (similar to those used in COVID vaccines), new BRD vaccines have been developed that trigger strong immune responses in cattle. After testing different vaccine vectors in the lab, one has shown particularly high performance. It has now been scaled up, and a cattle vaccination trial is underway.

Together, these advances are moving us closer to practical, effective vaccines that could make a real difference to the health and welfare of livestock and the resilience of farming in Scotland.

2022 / 2023

This project is developing new, safe, and effective vaccines to tackle some of the most serious livestock diseases affecting productivity and animal welfare in Scotland. In its first year, all objectives were successfully met.

Sheep scab vaccine: Researchers are working on a new vaccine to control sheep scab, a highly contagious disease that causes major welfare and economic problems. Promising antigens were produced in both yeast and bacteria, with bacteria chosen as the best system due to high yield and low cost. Early trials with one vaccine delivery system showed poor results, but switching to improved adjuvants delivered much stronger outcomes.

Innovative vaccine platforms: New technologies are being developed using plant viruses and bacteriophages to create virus-like particles that can carry livestock vaccine components. Several of these particles have already been produced and tested for quality, showing good potential as next-generation vaccine platforms.

Bovine respiratory disease (BRD): Progress has also been made in developing vaccines against two key viruses that trigger BRD in cattle - bovine herpesvirus (BHV-1) and bovine respiratory syncytial virus (BRSV). New vaccine vectors have been successfully designed and tested in the lab, with further evaluation planned.

Sharing knowledge: The project team presented their findings at international meetings, ensuring the research contributes to the global effort to improve livestock vaccines.

Together, these advances lay the foundations for new vaccines that could make a real difference to animal health, farmer livelihoods, and sustainable livestock production in Scotland.

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