Progress, challenges and opportunities in fish vaccine development.

In 2014 the contribution of aquaculture to supply food for human consumption overtook wild-caught fish for the first time. Despite improvements in the aquaculture industry, it has been estimated that as much as 10% of all cultured aquatic animals are lost because of infectious diseases, amounting to >10 billion USD in losses annually on a global scale. Vaccination to prevent disease is used routinely in finfish aquaculture, especially for Atlantic salmon (Salmo salar), while in a limited capacity (or not at all) in many other fish species due to lack of vaccines, poor performance or cost. There has, nevertheless, been impressive progress in fish vaccine development over the last 4 decades with 24 licenced fish vaccines now commercially available for use in a variety of fish species. These comprise whole killed, peptide subunit, recombinant protein, DNA and live attenuated vaccines. Challenges do, however, still exist as the majority of commercial vaccines are killed whole cell pathogen preparations administered by intraperitoneal injection. This may not be the optimal route to deliver some vaccines, but lack of effective adjuvants and basic knowledge on immune response has hindered progress in the development of mucosal vaccines. The cost of injecting fish may also be prohibitive in some countries leading to disease treatment (e.g. with antibiotics) rather than using preventative measures. It is important that these issues are addressed as the industry continues to grow globally. Exciting opportunities exist for rapid development of fish vaccines in the future, with continued reduction in cost of technologies (e.g. of whole genome sequencing), regulations changing (e.g. DNA vaccines can now authorised in Europe), the introduction of novel antigen expression and delivery systems (such as virus-like particles, VLPs), development of novel adjuvants and advancements in the elucidation of basic mechanisms of mucosal immunity. Development of effective mucosal vaccines and optimisation of their delivery will facilitate novel vaccine development, and enable the aquaculture industries in LMIC to use vaccination routinely in the future. In addition, effective use of emergency (autogenous) vaccines will assist in tackling emerging disease challenges.