The findings have produced a patented technology that makes the production of a live-attenuated vaccine possible. The process is now under review with key pharmaceutical companies, for possible licensing agreements, and makes the effective prevention and control of this devastating disease a real commercial possibility.
The success raises the possibility of being able to inoculate hybrid striped bass, tilapia, rainbow trout and other cultured species orally through feed, instead of having to inject individual fish—a prohibitively labour-intensive process for American farms.
Robust Response
Besides the economic benefits, live-attenuated viruses also stimulate a more robust immune response, meaning that the vaccine offers better protection from infection, said John Buchanan, a former researcher at the University of California and now chief of finfish research at Aqua Bounty Technologies in San Diego.
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| Hybrid striped bass being injected with an experimental live-attenuated vaccine. (Pic by John Buchanan) |
There are currently two vaccines on the market for preventing S. iniae infections - AquaVac Garvetil and Norvax Strep Si. Both are classical vaccines based on exposing fish to killed versions of bacterial pathogens. However, neither is approved for use in the United States. In addition, AquaVac is for use in tilapia only, and Norvax is most effective when fish are immersed in a 60-second dip initially; subsequent booster doses can be delivered orally.
The vaccine that Buchanan and UC San Diego pediatrics professor Victor Nizet are testing, in collaboration with Kent SeaTech, is based on mutating genes of the bacterial pathogen—not on killing the pathogen outright. These mutants have weakened virulence, but they can still infect fish, eliciting a strong adaptive immune response, in which antibodies to the real pathogen are created.
In the trials their vaccine has so far been administered through injection, which means that each fish has to be given a shot. However, the benefit of using live-attenuated vaccines means the medication could be put into the feed.
"The key is to be able to mutate a gene that does not wipe out the weakened pathogen’s ability to orally infect the animal. A vaccine that can be put in feed would have a huge potential advantage in cost,” said as Jim Carlberg, president of Kent SeaTech. “S. iniae is a ubiquitous disease and a fairly chronic problem,” Carlberg said. “It has a huge economic impact on worldwide aquaculture,” he added.
Gold Standard
Jeff Locke, a doctoral student with Nizet agrees. He used to work at Kent SeaTech, a large hybrid striped bass farm in Southern California and says oral delivery is the gold standard for aquaculture - it's what the industry needs.
About 26 species of fish are susceptible to S. iniae, which causes meningitis in fish. Infected fish are anaemic-looking, can swim abnormally and have 'popeye', caused by swelling in the brain.
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| Fish with “popeye” – swelling of the eye due to pressure build up in the brain. (Pic by John Buchanan) |
For US farms, there is no satisfactory treatment for S. iniae. Infected fish can be fed antibiotics, but sick fish often don’t eat. To treat outbreaks, which tend to occur at facilities where warm-water fish are kept at high density in recirculating tanks, Kent SeaTech has developed its own killed vaccine for S. iniae. However, it too requires that fish be individually injected.
Carlberg estimates that an orally delivered, live-attenuated S. iniae vaccine would generate revenues of about $10 million to $15 million worldwide annually. The savings to the global aquaculture industry could be worth 10 times this amount, he said.
Nizet, Buchanan and Kent SeaTech have now patented the technology that makes their live-attenuated vaccine possible. However, researchers with funding from California Sea Grant continue to study genes involved with pathogenesis.
Locke, for example, has identified two new S. iniae genes whose mutated forms represent potential new vaccines. Scientists are now hoping they can present a complete portfolio of potential mutants for development of a commercial product to a pharmaceutical partner.
“There may be one gene that contributes more to virulence than all the others,” said Locke.
The Economic - Approval Argument
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| Hand vaccination of hybrid striped bass at Kent SeaTech’s production facility. (Pic by John Buchanan). |
The USDA has already approved two other live-attenuated vaccines for other aquaculture diseases, so there is optimism that a live-attenuated vaccine for S. iniae would clear regulatory hurdles.
Buchanan said that economics is the reason pharmaceutical companies have not pursued USDA approval for the two killed vaccines now used in Asia.
“The cost of getting the vaccine approved in the United States is more significant than the size of the market,” he said. “Farms are allowed to make their own vaccines with bacterial isolates from their own facilities. That is what Kent SeaTech does."
An effective oral vaccine that could treat a variety of fish species would have greater value to American farms and therefore industry would pursue USDA approval, Buchanan said. Because the USDA is considered relatively strict, its nod would grease the regulatory process in nations that otherwise might be afraid of allowing a vaccine based on an infectious agent. “A killed vaccine is the norm,” he said.
Kent SeaTech is optimistic about the research outcomes. “I think there is an 80 percent chance that a real commercial product will come out of this research,” Carlberg said.
For more information about Sea Grant and its research and science projects go to www.csgc
February 2008
