Most of us relish an all-you-can-eat fish fry or salmon on the grill. Yet few of us consider the challenges inherent in producing these tasty entrees. Drs. Phillip Klesius and Julia Pridgeon of the United States Dept. of Agriculture, Agricultural Research Service, sums up the producers’ goal as ROI—return on investment. From hatch to harvest, fish face disease threats that cost the U.S. catfish industry alone an estimated $50-70 million annually. He and his colleagues are charged with developing safe and effective vaccines for prevention and control of economically important pathogens of aquatic animals, identifying effective mass delivery strategies for aquatic vaccines, and conducting research to support approval and licensing of new aquatic vaccines. An Ounce of Prevention Fish producers realize economic benefits from using vaccines to prevent disease rather than antibiotics to treat it. Least-cost large-scale administration of vaccines at the earliest life stages results in substantial disease prevention and more predictable and efficient production. In addition, only a few antibiotics are licensed for aquatic use, and they have withdrawal periods before fish can be harvested for human consumption. There’s also the fact that antibiotics are not effective against intracellular pathogens. Klesius notes that antibiotic use drops dramatically when vaccines are introduced. Take the classic case of the salmon industry in Norway. There the first aquatic vibrio vaccines were introduced in 1988. As more vaccines were introduced and vaccine use spread, antibiotic use plummeted. This pattern represented a net savings to producers without harming production levels. Developing Aquatic Vaccines Developing a safe and effective aquatic vaccine entails many of the same steps as producing a vaccine for other animals or humans. Researchers begin by studying pathogenesis, in particular categorizing the organism as bacterial, intra- or extracellular. They also search for the critical antigens necessary to provoke the desired immune responses. In this respect, modified live vaccines are ideal because all of the necessary natural antigens are present. Klesius admits, however, that choosing the right master seed isolate is as much art as science. The ideal candidate offers the broadest protection and can’t just be plucked from the American Tissue Type Collection of organisms. No adjuvant is required for modified live vaccines, as replication inside the animal ensures optimal immune system stimulation. Oil emulsion adjuvants pose particular problems for fish, causing adhesions in their flesh. One potential drawback of modified live vaccines is the theoretical possibility of reversion to virulence. However, Klesius notes that there has not been a break in two commercial modified live vaccines since their introduction in catfish industry.