HOW TO CHOOSE A VACCINE -
Some considerations to help limit disease in aquacultured fish

Adapted from Mitchell, Hugh. "Choosing a furunculosis vaccine: points to consider." Bulletin of the Aquaculture Association of Canada Edition 95-3 (September 1995): 30. [by Pamela Morris, 1996]

It is well known that disease threats can pose serious economic problems to any fish farming operation. Disease outbreaks may cause a loss of fish, poor feed conversions or product down-grading, which can mean a loss in revenue. The good news is that, for many diseases, there is help. The use of aquatic vaccines, combined with good health management techniques, can result in substantial disease prevention.

The key to controlling most diseases in fish is identifying the controllable risk factors in disease prevention, rather than putting considerable efforts into eliminating the disease-causing pathogen. It often happens that when a disease occurs, conditions have been created that favor the pathogen over the fish. Whether a fish becomes diseased when a pathogen is present depends on factors that include fish health, water quality and temperature, stocking density, pathogen load, vaccination status, handling practices, uniformity of grade, and proximity of neighboring farms which may experience different disease threats. Of these, vaccination status offers aquaculture producers an effective way to lower both the risk of disease in their fish and their cost of production.

Unlike antibiotics, which kill or stop disease-causing bacteria, vaccines stimulate the fish's immune system to produce antibodies that help protect the fish from disease. Once exposed to the vaccine, the fish's immune system reacts as if it were under attack by disease, producing antibodies that bind with the disease-causing bacteria and destroy it. This process is called a learned response, meaning that the immune system learns how to defend itself from disease by making bacteria-specific antibodies. When an outbreak occurs, these antibodies will help protect the fish from disease by giving its immune response a kick start. However, vaccines are not impenetrable shields, and the resistance they impart can be beaten if other risk factors are not considered. Even if a farmer vaccinates his/her stock, disease can still create problems if a good environment has not been provided and the immune system is overwhelmed.

As Figure 1 shows, "natural" disease resistance varies among individual fish within a population. This is represented in a typical "bell curve," where a small proportion of individuals has poor immunity to a certain disease, a small proportion has a high level of resistance, while the majority lie somewhere in between. Vaccination of a population shifts the curve to the right - most individuals acquire greater resistance, but there is still a spread in immunity. Depending upon the disease, it is conceivable that vaccination may also increase or decrease the variation of immunity within a population (as shown with the dotted lines). The farmer must decide whether it is beneficial to use vaccination to increase resistance to diseases, keeping in mind that all fish will not respond in the same way and that some fish will always be more susceptible to disease than others.

Outlined below are several factors to consider when choosing the best vaccine for a particular site. By following these guidelines and asking questions, a farmer can avoid confusion and make educated choices.

The decision to vaccinate is a dynamic one. The need to limit disease risk while increasing profit margins is specific to each farm in terms of location, equipment and management styles. There will always be changing disease threats as new diseases appear and current ones become less threatening. In addition, vaccines will continue to be changed and improved, and it will be up to the farmer to wade through all of the new developments and development claims in order to make the most cost-effective decision for his/her farm. However, a good vaccine should offer an acceptable return on investment.

An invaluable tool in the decision-making process is the cost-benefit analysis. The analysis can range from simple to complex, depending on the needs of the farmer. Used by many larger companies, cost-benefit analyses allow the farmer to take into account numerous factors, including vaccination man-hours, price of vaccine, and mortality. Using a simple cost/benefit analysis like the one shown in Figure 2 may help the farmer decide whether vaccination is the best solution for him/her.

 Figure 1. Disease resistance in a population of fish.

Administration Methods

There are three common methods of vaccination: immersion, injection, and oral. These methods vary in terms of ease of administration, cost, stress on the fish, survival rates, dosage control, the amount of labor involved, and the duration of protection. Ultimately, the decision concerning which of these methods to use is based upon a combination of actual and perceived risk, age of the fish, the farmer's own risk-aversion, and return on investment. Risk can be determined by the history of disease outbreaks at each site, including the persistence of various diseases.

It is generally accepted that injectable vaccines provide greater protection than immersion and oral vaccines because they allow for greater dosage control, which results in higher efficacy levels and a longer duration of protection. However, injectable vaccines tend to be more labor intensive, more expensive, and can cause damage to the fish if not administered with care. Nonetheless, injectable vaccines tend to make more economic sense for fish that fetch higher market prices. Figure 3 provides a quick comparison of the three delivery methods. In the end, the farmer will have to weigh all of his/her options in order to make the best decision.

A bacterin is a type of vaccine manufactured with a harmless suspension of killed or modified bacteria that stimulates the immune system to produce antibodies against one or more diseases. It is the predominant type of vaccine because of its cost-effective nature. Choosing the right bacterin for a specific operation depends on several factors.

One critical component of a bacterin is its antigenic mass, or the density of the killed bacteria in a bacterin. As a general rule, and to a point, the greater the antigenic mass, the better the immune response. There is a natural tendency for the farmer to want to include strains of several different disease-causing bacteria in one vaccine (a multivalent vaccine), to ensure that the product protects his/her fish from as many diseases as possible. However, given the same volume of vaccine, if there is no cross-protection between strains in a bacterin, then the more strains that are included, the less antigenic mass of each there is. This fact notwithstanding, it must be noted that there are times when the protection from a multivalent vaccine is preferable, if the manufacturer has carefully developed the bacterin to contain sufficient amounts of antigenic mass. (This information is discernible from field trial or other test data.)

Bacterial species can also work synergistically and actually help a vaccine work against a particular disease, even if the bacteria in the suspension do not cause the disease in question. Researchers believe that protection occurs in these cases because the bacterin stimulates the nonspecific part of the immune system. Other factors also affect the antigenic mass of bacterins, such as the addition of an adjuvant or emulsifier in an injectable vaccine (see next section). The farmer should evaluate the protection a monovalent vaccine offers against one disease versus the protection a multivalent vaccine provides against more than one disease when designing a vaccination program.

The manufacturing process can also impact vaccine efficacy. Many bacterins are produced by fermentation. Therefore, the quality of the finished product depends on careful attention to detail, or quality and consistency can vary markedly. Although most farmers do not have time to become experts in bacterin fermentation, they should try to understand what is involved in the process and to get a feel for the attention to detail that the manufacturer pays throughout the entire production process. Regulatory compliance is a good first indication of quality, but more careful scrutiny is wise. Look for careful documentation, procedural checks and balances, temperature control and variability, security and hygienic measures, and compliance with Good Manufacturing Practices (GMP) to help you evaluate the true quality of vaccine products.

Try to learn as much as possible about bacterins before making your decision. Ask questions about antigenic mass, cross-protection, and fermentation performance.

Figure 2. Cost-Effectiveness Model for Fish Vaccination [after Atle Lillehaug, Aquaculture, (1989) v. 83: 227 - 236]

COST = (Hmet x Wh) + (Vmet x Pvac) + Cadd
SAVINGS = Mno x RPSmet x Wfish x [Pkg - (FCR x Pfeed)]

Adjuvant Selection

The adjuvant is an important part of vaccines. Adjuvants can alter the immune response and enhance both specific and/or nonspecific parts of the immune response, which aids the vaccine in both strength and longevity of response. The response will depend on the type, amount, quality, consistency, and immune stimulatory effect of the adjuvant chosen.

Although adjuvants can be used in other types of vaccine, they are most commonly used in injectables. The most frequently used adjuvant for injectable vaccines is oil. An oil-adjuvanted vaccine can enhance the specific response to the bacterial antigen, using a "depot effect," whereby tiny, oil-encapsulated drops of antigen remain in the fish's body over a long period of time. The immune systems works to continually break down this foreign matter, and in the process creates protective antibodies that protect the animal for a sustained period of time. It is good practice to find out what type of oil your vaccine manufacturer uses, as the performance of different oils will vary. For instance, animal and vegetable oils have been known to break down in the fish's gut, significantly diminishing the depot effect and resulting duration of protection.

When a bacterin is used with an oil formulation, an emulsifier is often added to stabilize the mixture. Although excess emulsifier seems appealing because it can ease injection, it can also adversely affect depot and antigenic mass properties. Therefore, it should be carefully chosen. A farmer should be aware of these details and carefully consider the effect of added emulsifier on vaccine performance. Laboratory and field studies can both provide insight into how well a vaccine performs.

It is important to note that the use of injectable vaccines causes adhesions in the body of the fish. These adhesions are necessary for the immune response, but should not be so severe that they affect the quality of the meat or interfere with the fish's ability to digest food. Indication of a superior performing product is evidence that the vaccine residues and any adhesions clean out of the peritoneal cavity and do not adhere to the body walls or organs. Careful attention to detail when injecting will also reduce the risk of severe adhesions.

The ability to evaluate studies can prove to be an invaluable skill when choosing a vaccine. There are a number of important factors to examine when judging a vaccine performance study. These include, but are not limited to, degree of independence, raw data and statistics, and long-term protection.

Ideally, independent performance studies are preferred by fish health professionals. These studies are rare, however, as many investigators do not like doing research that will have them recommending one brand over another, potentially resulting in commercial consequences. In addition, the results of many studies are outdated upon release due to the constant change in vaccine development. Nonetheless, the farmer should attempt to obtain the most independent studies possible. The less control the manufacturer has over a study, the more independent it will normally be.

When at all possible, it is good practice for the farmer to obtain raw data and evaluate it him/herself, or solicit the help of a fish health professional or veterinarian in doing so. It is extremely important to obtain as accurate and reliable information as possible from a study in order to form an opinion on the worth of a vaccine. Statistics are important for formalizing studies and judging their results. It is critical that all fish that are tested are subjected to the same challenges and conditions. Ideally, the only variable should be that the test group receives the vaccine while the controls do not. Differences in such factors as water temperature, pen crowding, feed quality, timing and degree of challenge, number of vaccines versus controls, vaccine timing, dosage, and vaccination methods can affect performance studies, can skew the data, and can introduce bias into the study. Keep in mind that a bad study design can result in misleading conclusions. This can be even worse than not doing an experiment at all, because bad studies still appear to be scientific and are erroneous.

In addition, it is important to note whether studies were performed in a laboratory or in the field. It is best to have both data, as laboratory data will often not bear resemblance to field results and vice-versa. Finally, check data regarding long-term protection. Many studies gloss over this issue because of the cost involved in carrying out a study over a long period of time. The farmer should ask for the time period and other particulars of any study being examined.

Although farmers may be reluctant to share information with their peers, this is one good way to learn about which vaccines are really working and which ones are not. Whenever possible, get vaccine referrals from fish farmers, veterinarians, and fish health professionals. Ask what products they recommend, why they recommend them, and if they have experienced a problem with any specific vaccine. Any answers received should prove valuable in the decision making process.

Another useful resource in choosing a vaccine is the vaccine manufacturer itself. Whenever possible, meet the Sales and Research & Development staffs, learn the history of the company, and understand its goals and mission. Assess the degree of attention to detail that goes into vaccine research and production. Find a company that has a history of innovation and service to the aquaculture industry and is committed to fish health. The more global the manufacturer's scope, the more aware and prepared the manufacturer will be to help combat future disease threats. For, as demonstrated in the past with "Hitra" disease, for instance, the absence of a disease in one part of the world today does not mean it will not reappear there at a later time.

Vaccination has proven to be an effective and cost beneficial fish health management tool for the fish farmer. Keep in mind, however, that vaccines should not be thought of as a cure-all, but rather as a disease management tool that can help reduce and buffer the risks from other factors conducive to the development of a disease. The emphasis on controlling diseases should be directed to those factors over which a farmer can gain control. The decision regarding which vaccine to use is complex and should not be made without in-depth research. Use the information in this article to learn how to make educated choices about aquaculture vaccines.