The Development and Use of Fish Vaccines: History, Current Status, and Future
Aqua Health Ltd. / Novartis Animal Vaccines Ltd.
Bothell, WA, USA
Vaccines pre-date both modern medicine and the germ theory. The term originated from the Latin word "vacca," or cow, and can be traced back to 1796. In that year, Edward Jenner successfully vaccinated exposed children against smallpox using cowpox lesion scrapings. Eighty years later, only a couple of years after Koch proved the germ theory, Pasteur accidentally created the first live-attenuated vaccine against chicken cholera. Today, vaccines are common tools in human and terrestrial veterinary medicine. They are acknowledged to have dramatically improved livestock productivity, and even touted to have transformed modern society itself.
In agriculture, the reasons for vaccination are more varied than the traditional "protecting an individual from disease." Reasons include: protecting populations from outbreaks; controlling disease to an economic level; reducing the shedding of pathogens; raising the threshold of pathogen load required for infection; increasing the carrying capacity of a facility/system; and increasing the value of the fish (vaccinated animals can be more valuable than unvaccinated ones). Today, the development and use of vaccines for fish lag far behind that of human and other animals. Scientific literature on fish immune response did not appear until 1936, and demonstration of fish antibodies did not happen until 1942. After World War II, the "era of chemotherapy" stifled fish vaccinology until the 1960s, when the farmed trout and salmon industries in the U.S. Pacific Northwest stimulated renewed interest. Commercial fish vaccines were not successful until the mid-1980s with the explosive growth of the farmed salmon industry.
Today, in large part due to the relatively high value of salmon, these are the most widely used and successful fish vaccines with United States Department of Agriculture (USDA)-licensed and combination products for diseases associated with: Yersinia ruckeri, Aeromonas salmonicida, Vibrio sp., infectious pancreatic necrosis virus, infectious salmon anemia virus, Flavobacterium columnare, and Renibacterium salmoninarum. The most common application method is intracoelomic injection, although certain vaccines work well as immersion or even oral preparations. Vaccines for other aquaculture species are in development, or early stages of commercial use. These include: catfish, trout, halibut, sea bass, hybrid striped bass, tilapia, and even pet fish. The autogenous vaccine designation by the USDA is an extremely useful tool for allowing preliminary formulation trials with subsequent full licensure development. As with terrestrial production animals, it is important for the fish health professional to advise the client that vaccines should only be used within an integrated and comprehensive fish health program that involves the five basic disease control strategies: 1) vigilant surveillance and early treatment; 2) infectious pressure reduction; 3) risk factor minimization; 4) vaccination; and 5) good strain selection and genetic improvement programs.
The fish's immune system has some differences from mammals. For example: a faster acting but shorter duration innate (non-specific) system which, itself, may be more important in fish than it is to mammals, and a learned (acquired) system that may be simpler, less efficient, and less discriminatory. Furthermore, the ectothermic nature of fish causes ambient temperature to play a significant role in the immune response. The "ideal" development of fish vaccines has: a high level of protection; long duration of immunity and protection; freedom from reactivity; a high level of stability; and is suitable for mass vaccination in terms of price, ease, and route. To date, the most successful vaccines have been injectables with an oil adjuvant. The adjuvant acts as a carrier, has a depot effect, and is an immunostimulant. Unfortunately, occasional and sporadic side effects can be associated with these formulations, which manifest themselves in intracoelomic lesions such as: hyperemia, fibrinous to fibrotic adhesions, petechial to ecchymotic hemorrhaging, melanin deposition, ulceration, and myositis. Effects can cause downgrading at processing, poor growth and feed conversion, susceptibility to other diseases, and mortality. A scoring system has been developed to quantify these adverse reactions for tracking purposes. We are just beginning to understand some of the vaccine and exogenous interactions that contribute to these occurrences. These include pre-vaccination health status of fish, temperature at and after vaccination, volume of vaccine, concomitant diseases, adjuvant and emulsion used, anesthetic technique, injection technique/method and quality control, size of fish, photomanipulation, and smoltification status. There are numerous steps in developing a vaccine, each of which can stop the process if unsuccessful. These are: 1) isolating the microbiological agent associated with disease of concern; 2) characterizing and cultivating the microbiological agent; 3) infecting laboratory animals with confirmation of similar disease signs; 4) challenging model development; 5) performing preliminary "bench-top" fermentation experiments; 6) processing small-volume downstream culture; 7) performing wet laboratory vaccination, safety and challenge trials; 8) modifying and refining the above techniques; 9) scaling-up; 10) performing clinical field trials and safety laboratory trials; 11) producing regulatory submission and serial batches; 12) marketing, gathering feedback and refining the formulation. The basic goal of vaccine development and refinement is to remove the harmful and unnecessary components and maximize the immunogenic components. New vaccine technology on the horizon involves gene-deleted, sub-unit, vector, DNA, and synthetic preparations. As with agriculture, there is often considerable controversy and uncertainty about vaccine efficacy. Poor vaccine efficacy reports must be systematically investigated to determine the nature of the failure. Fish farmers, in making vaccination decisions, can use cost-effectiveness spreadsheet formulas. For vaccines to become more accepted as a standard tool in fish medicine, cooperation between the aquaculture industry, fish keepers, hobbyists, fish health professionals and the vaccine companies is essential.