Immune cellular dynamics predictive of vaccine protection in Atlantic salmon

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This project addresses the need for new and improved vaccines in Atlantic salmon, with emphasis on early determination of efficacy. We will reconstruct immune cell lineage temporal responses to vaccination at unprecedented resolution using single cell transcriptomics and apply the knowledge to help predict disease protection outcomes early post-vaccination. As a model, we will compare two distinct vaccine formulations to pancreas disease (PD) caused by salmonid alphavirus (SAV), which remains a major problem in aquaculture. A naïve cohort of fish will be split into three treatments: i) monovalent PD vaccine, ii) multivalent PD vaccine, and iii) PBS control (intraperitoneal injections). Fish will be split into non-lethal repeat sampling and lethal sampling groups, and sampled at common timepoints post-vaccination, before PD challenge and a final sampling for PD pathology. Head kidney, spleen, blood and peritoneal cavity leukocytes will be sampled to capture temporal development of the cellular immune response by single-nuclei RNA-Seq (snRNA-Seq). We will assess humoral responses by measuring development of antibodies to SAV. Our study design allows for assessments of PD pathology (heart, muscle and pancreas lesions; viraemia, tissue viral load) and antibody data to be correlated with snRNA-Seq data on an individual level. We will generate >1-million single-nuclei transcriptomes spanning 168 samples (50,000 reads per nucleus). snRNA-Seq data will be analysed to describe immune cell lineages/subsets and their responses to the PD vaccines, with trajectory inference used to describe B and T cell differentiation pathways. We aim to identify immune cell lineages and cell-specific marker genes correlated with PD protection across the post-vaccination timecourse. Finally, we will develop, validate and benchmark a unique Fluidigm BioMark qPCR array for high-throughput, cost-effective measurements of cell-specific markers that correlate strongly with PD vaccine protection.