Abstract

Bacterial outbreaks pose major challenges to global fish aquaculture, causing high mortality, economic losses, and threatening environmental balance and social stability through antibiotic overuse, ecological disruption, and reduced food security. One prominent approach to combat these diseases and reduce mortality involves vaccine development. In this context, cell lines and primary cultures provide a straightforward and economical model to evaluate vaccine efficacy. To determine the uses of cell culture in the development of fish vaccines against bacterial pathogens, this study systematically reviews the current knowledge of cell lines and primary cultures in fish. We conducted a systematic literature search across Web of Science, PubMed, and Scopus databases following PRISMA guidelines. Out of an initial 1123 studies published up to August 2024 screened for eligibility, only 24 met the criteria for inclusion based on relevance to vaccine development for bacterial fish pathogens. Our review identified 16 cell lines and four primary cultures with potential applications for vaccine development in fish species such as rainbow trout, olive flounder, Asian seabass (barramundi) and Atlantic salmon. Key applications of cell lines and primary cultures in vaccine development involve immunostimulatory and immunomodulatory effects (9/24; 37.5 %), cytotoxicity testing (8/24; 33.3 %), and DNA vaccine fabrication via transfection (6/24; 25 %). However, our findings reveal limited availability of cell lines in biobanks (ATCC, JCRB and ECACC), which hampers result reproducibility. We conclude that, despite the high potential of cell lines and primary cultures for vaccine development, these models are established as routine tools in only a few fish species.