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United States Department of Agriculture

Agricultural Research Service


item Klesius, Phillip
item Evans, Joyce
item Shoemaker, Craig

Submitted to: Panamerican Congress of Veterinarian Science
Publication Type: Proceedings
Publication Acceptance Date: April 19, 2000
Publication Date: September 11, 2000

Technical Abstract: The impact of the communicable diseases remains as one of the major limiting factors to increased economic growth of fish farming. Among these communicable diseases are those caused by Gram- positive and -negative bacteria (Plumb, 1999). The stress on fish caused by intensive farming practices and the development of antibiotic-resistant bacteria are among the major reasons for the increased frequency of communicable bacterial disease outbreaks. In Japan, the frequent use of antibiotics has resulted in the development of resistant bacteria(Aoki,1992). In Norway, the use of vaccines against highly communicable species of Vibrio has resulted in a significant reduction in the use of antibiotics(Markestad and Graves, 1997). In the U.S., governmental regulations and the research and development costs associated with antibiotics have curtailed the introduction of new antibiotics for use by fish farmers. The best alternative method to chemical control is to prevent communicable diseases by stimulation of the fish immune system by vaccination and use of immunostimulants. Further, due to the environmental issues concerning the application of chemotherapy in fish farming, these biological control methods offer a safer and more effective means. This article presents the concepts and strategies of vaccination and immunostimulation for the prevention of highly communicable diseases in fish farming. The immune system of fish can be divided into acquired and natural immunity. Acquired immune system is mediated by antibody and memory and cytotoxic cells and natural immune system is mediated by lytic enzymes, phagocytic cells and nonspecific cytoxic cells. Vaccines stimulate the acquired immune system to produce specific antibodies and immune cells. These antibodies and cytotoxic cells act separately and in conjunction to rid the body of the communicable agent. Immunostimulants act on the natural immune system to activate its nonspecific lytic enzymes and nonspecific cytotoxic cells. These humoral enzymes and cells can act independently or together to fight the infectious agents. Activation of the acquired immune system provides long-term protection with memory and the activation of the natural immune system provides short-term protection with no memory for infectious agent. The strategic applications of vaccines and immunostimulants must include the characteristics of the target disease and of the protective immune responses, duration of protective immunity, epidemiology and the characteristics of the aquaculture system itself. For example, protection against a toxin-producing bacterium requires the use of an anti-toxin type vaccine and not the use of an immunostimulant. Antibodies must neutralize the toxin to prevent the disease. The objective of vaccination is to protect the fish before exposure to the infectious agents encountered in their production system. There is only limited numbers of licensed vaccines and most of these are for use against communicable bacterial diseases (Adams et al.,1997). Vaccine types include killed, modified live and genetic. The killed vaccine is the most common type used in aquaculture and this type of vaccine is administrated by injection. Modified live vaccine is less common, however this type of vaccine can be administered by immersion, orally administered and by injection. Genetic (DNA) vaccines are experimental and this type of vaccine is administered by injection. The choice of the type of vaccine to be used includes the characteristics of the target disease, characteristics of the protective immune response, the age of the fish, costs, safety of the vaccine and the duration of protection needed. For example,injection administration of a killed -type vaccine is expensive and used primarily in larger sized fish. Modified live vaccine is easly administered by immersion of the fish in the vaccine at a much lower cost per fish. Oral delivery of a modified live or killed vaccine offers an approach that would allow vaccination of fish at lowest cost per fish with multiple vaccine administrations. The ideal vaccine is safe, effective, convenient and affordable. The identification and characteristics of the protective antigens or the virulence factor(s) of the bacterial agent is the starting point in the development of a vaccine. Next, the nature of the protective immune response needs to be determined to whether it is dependent on antibody or cytotoxic cells. The performance of the vaccine, its safety and effectiveness under field conditions is the next step. The final step is the 3-5 years needed to license and manufacture the vaccine. We (Klesius and Shoemaker, 1999) recently developed a modified live vaccine against enteric septicemia of catfish (ESC) that meets the ideal characteristics of a fish vaccine. This vaccine stimulates the cytotoxic cells of the acquired immune system after immersion administration of fry or fingerlings. This vaccine is licensed and is being manufactured and distributed in the U.S. for the prevention of ESC. Another vaccine, we(Klesius, Shoemaker and Evans, 1999) have developed is against Streptococcus iniae, a major disease problem of tilapia. S. iniae is highly communicable bacterial pathogen known to cause serious disease problems in 11 species of warm-water fish. This vaccine is a killed type that consists of whole killed bacterial cells and a toxoid. It is administered by injection and provides effective protection against streptococcosis caused by S. iniae for 4 months. The immune protection is believed to be provided by antibody and phagocytic cells. Fish vaccines require the standards of governmental regulations to ensure their safety and effectiveness before their use by fish farmer(s). Immunostimulation of the immune system helps to provide greater protection against bacterial pathogens in culture system, especially when fish are under stress. Suppression of the immune system is likely to occur in the intensive interactions between fish and their culture system. These environmental and behavioral stresses are the cause of suppression of the immune systems (Van Musiswinkel et al, 1999). Often immunostimulants are used to overcome the negative effect of stress on the immune systems of fish in intensive production system. Also, immunostimulants are employed to enhance the effectiveness of a vaccine, especially under stressful conditions in which immune systems are suppressed. Immunostimulants are usually chemicals or products of microorganisms and plants (Anderson, 1992;Ducan and Klesius, 1996). An example of a chemical type of immunostimulant is levamisole. Vitamins and mineral supplements are considered to have immunostimulant properties (Sealey et al., 1997). The most common microorganism and plant type immunostimulant are beta-glucans(Klesius and Shoemaker, 1997). There has been a surge of interest in the use of immunostimulants in the last 10 years. The most commonly used immunostimulant is Beta-glucans. The chemical properties of Beta-glucans vary considerably depending upon source and extraction method. The immunostimulant properties of Beta-glucans appear to be dependent of its solubility, chemical structure and formulation. A number of Beta-glucan products are commerically available under various trade names. The effectiveness of Beta-glucan is dependent on how they are administered, dosage and freqency given, species, age and health of fish, production system and disease characteristics, and types and exposure load of infectious agents present in the production system. Immunostimulants are a tool in health management practice and not a magic bullet to control bacterial diseases by themselves. Currently, most immunostimulants are not a governmental regulated biologic but considered a feed additive by many governmental regulatory agencies. Regulations similar to those used to ensure safe and effective vaccines may be needed for immunostimulants. Many manufacturer

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