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

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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