The changing landscape of the vaccine industry and our preventative strategy (Proceedings)
Generalities of vaccination and vaccine formulations
The deliberate induction of active immunity to an agent by exposure to the agent or to non-replicating components, with the intent of inducing protective immunity to challenge with a virulent infectious agent, is termed "vaccination". Actively acquired immunity is that provided by an antigen specific response of the challenged host's own immune system in response to materials recognized as non-self. Active immunity is usually long-lived with generation of memory cells. While we, as veterinarians, will never be privy to all of the information due to proprietary protections, we can nonetheless develop rational strategies for vaccine use based on the data we have. This data should be used to achieve the goals of maximizing the effective immune response. By maximizing the immune response, the secondary goals of safety and cost can be met. Expectations a practitioner should have in mind when choosing a vaccine formulation: First and foremost a vaccine should provide protection against virulent challenge. Whether or not a vaccine actually does this, is at the heart of most of our vaccine conundrums and reflects the degree to which a currently marketed vaccine has undergone efficacy testing (addressed in the next section). Second, a vaccine must induce a protective immune response among essentially all members of a population. Premarketing efficacy testing should demonstrate an efficacy level of at least 90-95% preventative activity. Many currently marketed vaccines do not provide this level of efficacy overall or within target populations. Knowing these deviations from this goal is important for effective vaccination. Third, a vaccine should induce memory for long-lasting protection. Most animal vaccines do have to show induction of memory. Many are simple formulations that do not induce long-lasting protection. Fourth, a vaccine formulation should not be susceptible to rapid evasion by strains of an infectious agent that vary antigenically from the type strain used in development of the vaccine. We are fortunate in the equine industry to not have rapid expansion of new strains in many of our diseases, even influenza. However, because of the regulatory barriers to frequent updating of vaccines, the industry is susceptible to development of new strains of many diseases which could result in reemergence of disease. Fifth, it must be safe and without serious side-effects. In the case of attenuated live vaccines, this includes no reversion to virulence. Sixth, vaccine use should not cause confusion in the diagnosis of the active infection. Unfortunately vaccines are developed with little regard to this expectation and frequently it is the diagnostic community that comes up with new testing strategies in response to a vaccine. Seventh, vaccine should be stable and easy to transport. Unfortunately, for most veterinarians, this requirement often leads to biasing of vaccine use only toward killed vaccines. Many killed vaccines are excellent, however, there are other more recently developed vaccines that a far superior and the main barrier to their widespread use is the actual product formulation. If this is the only barrier to use of a superior vaccine, then clients are ill-served. Eighth, the vaccine should be affordable. The definition of affordability is ill-defined. If one chooses to use a shorter acting vaccine because it is less expensive than a longer acting vaccine, then this is not a less expensive strategy for the client due to lack of protection or the need for more frequent veterinary contact.
What a vaccine MAY NOT do is eradicate a disease. Eradication of disease through vaccination is a rare event. These diseases generally have little subclinical or chronic states so that infected animals can be easily identified and separated from susceptible populations: the best example is small pox vaccination. These diseases usually have a short incubation period and organism spread is usually confined to the period of clinical signs. Eradicable diseases usually do not have wildlife reservoirs. Thus, a serious discussion with clients on the expectation that vaccination will minimize disease but not erase the disease or totally mitigate the risk of disease is required. An example of these are equine respiratory viruses. Vaccination against many of the respiratory diseases, decrease severity of disease and decrease viral, but these common viruses will not eradicated through vaccination.In general a vaccine should NOT be used for treatment! There are many times during the incubation and onset of disease that active priming of the immune response at that time is futile and may even be deleterious. For example, we have recently published evidence that horses vaccinated against WNV within two weeks of exposure actually had a higher chance of exhibiting clinical signs if they developed WNV within this time period (Rios LV. Et al. 2009)
Vaccine quality can vary due to the enormous number of variables which ultimately define an effective immune response. The type of antigen is the most important of these; type-proteins > carbohydrates > fat, complexity, size, dose. Thus the industry often expects very basic preparations composed of compounds that may not be of the best composition because of the variability of the immunogenisic properties of the organism itself. For example, rabies and tetanus, a viral immunogen and basically a protein are very good immunogens while others, may require adjuvants or modifications of the immunogen itself to enhance its basic response when inactivated.
Vaccine response overall and the type of response varies according to the route of inoculation. Most equine vaccines are deep intramuscular and have historically been developed as such because of the possible cosmetic outcomes associated with reactions. Whether or not this is true, intramuscular administration is inherently less immunostimulatory than subcutaneous. This is one of main reasons why many killed and live vaccines have adjuvants. Oral and nasal vaccines are an excellent strategy for stimulation mucosal immunity throughout the body. However, an oral or nasal vaccine may not produce high levels of IgG systemically. For example, if the goal in vaccinating broodmares were to produce colostral IgG, then an intranasal vaccine would be counter indicated because these vaccines induce primarily local musosal immunity.