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Infectious diseases are one of the most significant threats to the economic stability and future expansion of finfish aquaculture. Vaccination is widely considered the best prevention strategy and, therefore, much research effort is focussed upon the development of new and more efficacious fish vaccines with easier, less labour-intensive methods of administration. Presently most research groups use a vaccination-challenge strategy to evaluate immune protection, monitoring the expression levels of immune genes in terminally-acquired tissue samples, usually at the mRNA level. However this approach requires large numbers of experimental animals to obtain sufficient statistical power (due to inter-individual variation) and provides only limited information on the nature and kinetics of the protective response. In an effort to overcome these barriers, we are developing a proteomics platform to allow the rapid, repeatable and accurate quantification of immune proteins in minimally-manipulated blood plasma samples. We are currently optimising targeted and shotgun mass spectrometry approaches, performed on Q Exactive hybrid quadrupole-Orbitrap system, using rainbow trout (Oncorhynchus mykiss) as our study model. These new approaches are being implemented alongside a non-lethal sampling technique, enabling us to study global and target-specific changes in immune protein levels in individual animals over the course of an immune response. We will present our latest data and discuss how our approach offers a more accurate and richer understanding of the fish immune response, while dramatically reducing the number of animals …