Enhancing the efficacy and ease of application of existing endemic livestock disease vaccines via novel adjuvants and delivery systems

Endemic infectious diseases of livestock cause major financial losses and threaten food security, animal welfare, and public health. Vaccination is a highly cost-effective tool to help prevent, control, and eradicate diseases. However, many vaccines currently used to prevent and control endemic livestock diseases (ELD) are suboptimal. While they may help protect animals from suffering disease, they may not effectively control the disease-causing microbe (pathogen). This allows pathogens to be transmitted to other animals and potentially to mutate as they replicate, which makes them more resistant to vaccines. In addition to these inherent shortcomings, there are practical issues of storage and administration of vaccines on-farm that require improvement to optimise the benefits to users and animals from vaccination. This project aims to take advantage of recent advances in vaccine formulation and delivery to devise strategies that could make ELD vaccines more effective and easier to administer. We will use vaccines for control of the porcine reproductive and respiratory syndrome virus (PRRSV) as a test case. PRRSV is responsible for one of the most economically important diseases affecting the global pig industry and is a priority disease for the UK pig sector. Vaccination is a cornerstone of PRRS control, but improved vaccines are urgently required.

The project is a collaboration between leading UK veterinary bioscience, social science, and stakeholders. Using a co-design and participatory approach, we will work with vaccine companies and selected producers, their veterinarians, and wider stakeholders to ensure that the research addresses their concerns and meets their needs with respect to on-farm delivery and use of vaccines to support a drive for improvement. By taking soundings from stakeholders, we will seek to understand, and therefore take into account, their concerns and needs as regards on-farm vaccine use. We will explore issues around the acceptance of new vaccines and delivery devices. We will then conduct a 'proof-of-concept' study to test whether new formulations of an existing PRRSV vaccine, delivered by innovative devices, provides enhanced protection, whilst being simple and practical to administer. Finally, we will take our findings back to producers via virtual workshops to obtain their feedback, which will help shape the future research and development of the approaches. This project will help deliver improved vaccines and their adoption, which will aid the prevention and control of ELD. Consequently, this project should lead to enhanced livestock health, welfare, and productivity, and reduced antimicrobial use. Whilst the most immediate benefit will likely be in the control of PRRSV, this project has the potential to have a wide impact by informing efforts to develop improved vaccine/formulations for other diseases of both livestock and humans.

Control of endemic livestock diseases (ELD) is hindered by the suboptimal immunogenicity and efficacy of existing vaccines. In addition, practical issues of storage and administration on-farm can negatively impact on the efficacy of current vaccines and present barriers to the development of more efficacious vaccination strategies. We will exploit recent advances in knowledge and technologies to improve existing ELD vaccines. This includes vaccine adjuvants and formulations; delivery routes and immunisation regimes, including mucosal immunisation either alone or in combination with parenteral immunisation; and automated delivery devices. By combining these three elements, we anticipate achieving significant benefits in terms of: immune responses tailored to provide stronger protection; improved vaccine stability; needle- and error-free dosing; and cost savings through dose sparing. Using a co-design inspired approach, we will work with vaccine companies and selected producers, their veterinarians, and wider stakeholders to ensure that the research addresses their concerns and meets their needs with respect to on-farm delivery and use of vaccines. We will next use PRRS as a test case and determine whether a 'prime and pull' immunisation strategy combining a solid dose implant live-attenuated PRRS virus prime, and an inactivated PRRSV with mucosal adjuvant boost administered by an automated jet device can enhance protection against experimental infection. By sharing these results and demonstrating the delivery devices to stakeholders we will gain feedback to help shape further development. The proposed approach is novel by exploiting and combining recent advances in vaccine formulation and delivery to address the shortcomings of existing vaccines, including their application. This project has broad translational potential which could lead to improved vaccine/formulations for diseases of both livestock and humans.