Immune cell dynamics predictive of vaccine protection in Atlantic salmon

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Salmon farming is a key UK food sector, producing more than 200,000 tonnes of fish in 2019, representing the top national food export. This sector provides an economic contribution of £1.8-billion per year and is responsible for around 8,000 jobs, concentrated in rural regions of Scotland. The salmon industry has ambitious growth targets, aiming to double its contribution to the economy and job market by 2030. This ambition is hindered by negative impacts caused by infectious disease to fish welfare and the environment, with a range of viral diseases being a major current problem. To help the sector grow sustainably, such challenges need to be overcome with the support of scientific innovation.Viral disease outbreaks on salmon farms cause major financial losses and welfare problems. There further exists a continuous threat of new viral diseases entering aquaculture systems due to climate change. There are no treatment options to control salmon viral diseases, and vaccination remains critical, with several viral vaccines on the market for commercial use. Over 50 million fish are vaccinated in the UK each year. While this effectively controls bacterial diseases, viral disease remains an unsolved problem. Consequently, the development of new and improved vaccines to control viral diseases in farmed salmon remains critical.Developing effective vaccines requires extensive fish use, with hundreds of animals killed per trial to gain data on efficacy after disease challenge. The whole process is expensive and time consuming. Methods that accelerate vaccine development, while substantially reducing the number of animals killed, will represent an important step forward in terms of animal welfare and cost savings. Fish share many components of the immune system with mammals leading to protective responses following vaccination. However, we have a poor understanding of the role played by the large diversity of different immune cell types in protective immune responses and immune memory in fishes. New technologies allow us to quantify global gene expression in individual cells (so-called 'single cell transcriptomics') and hold exceptional promise to transform our understanding of cell diversity responsible for immune protection following vaccination in fish. Our aim is to create a large up-step in understanding of how vaccination against a major problem viral disease (called pancreas disease) leads to immune protection through dynamic changes in immune cells. We will apply single cell transcriptomics to samples taken from a carefully designed vaccination experiment, designed to link early changes in immune cell expression to immune protection generated over months. The first major aim is to describe the full diversity of different cell types in the major tissues of the salmon immune system, including how these cells respond to viral vaccination. We will compare two registered pancreas disease vaccines with very different formulations to understand cellular mechanisms leading to differences in disease protection. The second major aim is to identify immune cell types, and specific marker genes for these cells, correlated with vaccine protection. A final objective is to use the results to develop a cost-effective platform that can be used to accurately predict disease protection early post-vaccination.In addition to creating major knowledge advancement on the cellular basis of protective immune responses in fish, the results will have applications in vaccine research and development, opening up strategies to assess vaccine efficacy using faster more cost-effective strategies and fewer animals. This may lead to improvements in vaccine design and testing that can positively impact the sustainability of salmon aquaculture while promoting fish welfare.