By Hugh Mitchell, MS, DVM (Guest Columnist)*
The answer isn’t simple. Trying to explain what vaccines are and why they work (or don’t) can come across as evasive or “wishy-washy”, with the result being the rejection of what is an important tool for a fish culturist. This is not new to fish vaccines. In the classic veterinary text book: “Herd Health: Food Animal Production Medicine” (2nd edition), Radostits et al. state: “The veterinary practitioner is often asked for advice about the use of vaccines for the control of infectious diseases of food producing animals. There is probably more controversy and uncertainty about the efficacy of these vaccines than about almost any other topic in livestock production”.
How do vaccines work?
There doesn’t seem to be the same ambiguity afforded to antibiotics or other fish health chemotherapeutics, so why vaccines? Vaccines are older than germ theory and have revolutionized medicine (since 1796!), so it isn’t as if they are new technologies that have to be embraced. There are several factors involved in why vaccines are met with confusion, and therefore prevented from more widespread use in fish culture, versus terrestrial livestock. Of course, one of these is the fact that vaccines are preventative and the action you should see if they work is a passive one: if they work, the fish don’t get sick (or as sick). Important concepts to understanding vaccines include:
1.The mode is indirect and not like a chemical which works directly on a bacteria or parasite. Vaccines work on the immune system, which in turns works on the bacteria or virus. The interaction of the immune system with foreign material is extremely complex and we don’t completely understand it in human medicine, let alone in fish. The immune system reacts to what it considers foreign, while a pathogen (bacteria, virus, parasite, etc.) tries to not appear foreign. It is a “cat and mouse” game in which the immune system, unfortunately, often over- or under- reacts (e.g.: allergies or cancer). The reaction of the immune system is also markedly modified by the environment acting on the fish and the fish’s physiology. So, the same stress that is often instrumental in bringing on a disease situation can also inhibit a vaccine-prepared immune system to optimally function, despite the vaccine being an effective one.
2.Vaccines can provide some measure of worthwhile protection, but this may be overshadowed and undetectable if one or more of the other 4 important areas are way “off-kilter”. Related to mode of action, is that – especially with mature fish culture facilities - diseases are not always easily solved with “silver-bullet” cure all answers. Solutions require integrated and multi-factorial approaches. Figure 1 depicts the fundamental areas that need to be addressed in order to keep fish healthy on a farm, as bricks in a “disease dam”. The relative importance (“size of each brick”) varies depending on the disease and the situation (1 a, b &c).
3. A vaccine working on an individual is different than one working on a population. We are accustomed to thinking that if you vaccinate, the animal (or human) won’t get the disease. Generally, this is what we experience (except maybe with the flu vaccine). However, on a population level (e.g.: group of fish) there are always non-responders (even with the best vaccines) and the proportion of these can vary based on the vaccine, the factors mentioned previously and possibly individual genetics. In fact, a vaccine may not protect an individual in an at-risk situation, but may protect a group of fish from an outbreak. This is part of what is called the “herd effect”, where the immunity of the herd actually will protect non-responders by inhibiting the pathogen load from getting in and building up to cause disease. Furthermore, a vaccine may not necessarily control a disease entirely in the population, but just down to a level that is economically acceptable for the farmer.
4.Added to this complex picture, there IS a difference between how well different vaccines work depending on the mode of application, and specifics about the vaccine itself, including but not limited to: how it was grown (or how an identified immunogen is propagated), killed, processed, assembled, and what was the nature and amount of any adjuvant that was included, as well as other constituents. This is as much of an art as it is a science and vaccine technology is mostly unpatented with closely guarded know-how from a relatively short history of use in fish. So, given two similar vaccines, there can be a difference in how much one can contribute to the disease dam (“size of brick”) of Figure 1. The disease organism itself can be responsible for a large degree of the inherent efficacy. Some bacterins are impressive in how they work with simple “grow and kill” recipes (e.g.: Typical Yersinia ruckeri or Vibrio spp.) -almost approaching a “silver bullet” status. Others, such as Aeromonas salmonicida (associated with Furunculosis) take a little more in terms of growth methodologies, downstream processing, strain selection, etc., and even then efficacy is not near what the previous examples are, with injection often being the only method that provides an adequate measure of protection versus immersion. Some bacteria and viruses continue to elude efforts to develop an adequate cost-effective solution (IHN in trout; Aeromonas hydrophila). Some may need multiple applications (“boosters”) in order to show any effect.
Should a farm try a vaccine
So, how is a farmer to wade through all of the above complexity and decide whether to try a vaccine strategy for a particular disease? First of all, most vaccines and iterative vaccine formulation improvements are the products of work done in “wetlabs”, where vaccinated and non-vaccinated fish are challenged with the disease organism. Although useful as a baseline, farmers need to understand that wetlab efficacy data does not necessarily translate to the “real world”. There are many instances of successful wetlab vaccines taken to a production environment where they fail miserably. Most of the reasons for this center round the above discussion regarding the immune system and its interaction with the pathogen and the environment, including all the other factors discussed in Figure 1, which are difficult to duplicate in an in vitro wetlab setting.
Despite the technology employed, the mode of application or the regulatory status, the best approach is to KEEP IT SIMPLE and remember what that means: Will the cost of the vaccine and what it takes to administer likely provide a pay-back, or at least pay for itself?
With today’s “on-the-hip” technology (smart phones, tablets, etc.) and the widespread use of spreadsheets, it is relatively easy to do a cost-effectiveness scenario in order to help in the decision-making process. Figure 2 from Lillehaug’s 1989 paper (Aquaculture 83: 227-236) provides an excellent starting point with a formula for costs and savings that can be put into a spreadsheet and modified to suit a particular circumstance. The power of this approach is that a farmer can put in various vaccine efficacy scenarios in order to see how a vaccine would have to work in order to pay for itself, and what level of protection it would have to reach to provide an acceptable payback (which can vary between roughly 1:2 or 1:10 in dollars spent:gained). The author has often used this approach with clients who would like to try to incorporate vaccines, but are having trouble determining whether it is worth it. For example, the savings:cost formula for one farm and one disease was even ($0) if the RPS (Relative Percent Survival) level was 10% (relative number of vaccinated fish that would have otherwise died to the disease). At the 50% RPS scenario, the farmer would save/gain $500,000, and at the 90% RPS scenario, the farmer would save/gain $1,500,000.
The obvious question is how does a farmer decide what might be a reasonable RPS to expect from a vaccine, in order to plug in to the formula to help in the decision-making process of whether to try or not?
There are no hard and fast rules, but if the RPS needs to be extremely high (>75%) in order to achieve break-even with an unknown vaccine (costs=savings), then expecting a satisfactory result might be a bit of a stretch. A good rule of thumb would be to consider trying a vaccine if the breakeven of the cost-savings spreadsheet is 20% or less (this figure will vary with what the farmer is comfortable with, financial status, risk aversion, etc.). This could be interpreted that the vaccine only has to perform 20% or better at your facility versus not vaccinating in order to pay for itself. That isn’t too much of a stretch. If the cost-savings breakeven is 5%, that is almost an easy decision (why not try?), or if it is something like 95% (too much to expect, not much pay-back headroom and probably not worth it).
Of course if there is evidence that a particular vaccine is a particular long-shot (hasn’t been done before despite numerous efforts) or if there is trusted evidence of solid protection in the wetlab, and even some positive production performance from other situations, then this “action” RPS level might be adjusted up and down accordingly.
Which vaccine option to try?
As for which vaccines to choose from, this will vary with respect to what country you are from (regulations), or method which is feasible for you to employ (oral, immersion, injectable).
From a regulatory point of view (depending on your country), types of vaccines that you can access fall into several categories, in approximate order of the flexibility of their formula these are: fully-licensed; conditionally licensed; experimental; autogenous; and non-licensed (regulatory exempt).
1. Fully-licensed vaccines are generally only available for the major species and major established diseases because of the cost to develop and manufacturer in a licensed facility, with mandatory batch safety and potency tests. These measures assure consistency (safety and potency), but may not translate to field efficacy particularly if there are geographic strain differences of the pathogen(s). Farmers are well aware of licensed vaccines with questionable field performance. However, for those established diseases in large industries (eg: salmon), licensed vaccines have excellent track records. They have been instrumental in driving current fish vaccine technology.
2. Experimental and conditional vaccines are produced under the similar standards, but efficacy and sometimes safety in the field, aren’t known. They are used by farmers with the understanding that they are “on their way” to being licensed. There usually have been several successful wetlab studies that has brought a vaccine to this point of development. Paperwork is often required as these are pre-licensing studies.
3. Autogenous-licensed vaccines were created realizing the dynamic nature of disease and how licensed products couldn’t be changed quickly enough or cost-effectively to keep up. They must be produced in an autogenous-licensed facility and must be tested for short-term safety but not any kind of potency or efficacy (that is up to the farmer to assess). For fish – a minor species, even the autogenous regulations required for production limits their usefulness as a cost-effective option.
4. Regulatory-exempt vaccines (US). These can only be made by animal owners for their own animals, or by licensed veterinarians for their clients. The advantage is maximum flexibility and customization for a situation and facility, with the disadvantage of being: limited quantities and varying quality. They are more of a medical approach between the veterinarian and farmer, who together come up with a solution that works and is safe on the particular farm. Also, unless a veterinarian (whose license is on the line) or animal owner (whose livelihood is on the line) has any familiarly or expertise with vaccines, experimentation may not be a prudent choice. This avenue is an important mechanism that recognizes the inherent safety of most vaccines, and provides a mechanism for initial field use, which may lead to registered products. These cannot be made in licensed facilities under the US Code of Federal Regulations pertaining to animal vaccines.
The major mode of application is the other important consideration (oral, immersion or injection). Although every farmer prefers the oral route, as it is the least effort and stress on the fish, these are usually the least efficacious and gives the shortest duration of protection. In fact, for most vaccines to date, a gross generalization (there are exceptions!) might be that the ease (and expense) of application (oral > immersion > injection) goes hand in hand with the least to best duration and efficacy (injection: best). This does enter into the cost-savings formulation discussed previously and can influence whether it is worth considering vaccination.
In summary, vaccination is an important, yet underutilized tool in fish culture. It is a complex product, with equally complex interactions with the host, environment, and disease organism. With this understanding and using cost-savings metrics to help in the decision-making process, farmers should be encouraged to not ignore this important weapon that may be of substantial help in disease control and reducing overall aqua-business risk.
Hugh Mitchell, MS, DVM is an aquaculture veterinarian with more than 25 years of experience, who provides services and fish health tools to fish farmers across the US and Canada. His practice is AquaTactics Fish Health, out of Kirkland, Washington, specializing in bringing a comprehensive professional service/product package to aquaculture, including: vaccine solutions, immune stimulants, sedatives, antimicrobials and parasiticides.