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DNA vaccines for fish: Review and perspectives on correlates of protection.

Recently in 2016, the European Medicines Agency (EMA) recommended granting a marketing authorization in the EU for "Clynav," a DNA vaccine against salmon pancreas disease (salmonid alphavirus-3). Generally, DNA vaccines induce both early and late immune responses in fish that may be protective against disease. Several transcriptomic approaches have been performed to map immunome profiles following DNA vaccination, but the precise immune mechanism(s) that is responsible for protection is not known, although reasonable suggestions have been made. The current review includes an overview on main transcriptomic findings from microarray experiments after DNA vaccination against VHSV, IHNV, HIRRV and IPNV-with considerations of what can be considered as correlates of protection (CoP) or merely a surrogate of protection. Identification and use of correlates of protection (COPs) may be a strategic tool for accelerated and targeted vaccine design, testing and licensure. General rules on what can be considered as CoPs can be extracted from past knowledge on protective immune responses following vaccination that induced protection. Lastly, there will be an overview on non-viral molecular adjuvants that have been exploited to obtain higher vaccine potencies and efficacies.