DEVELOPING A VACCINATION PROTOCOL
The use of vaccines to prevent and control infectious disease is an accepted and necessary method of preventative health care in veterinary medicine. Vaccination of every patient against every possible disease on an annual basis carries risks and may be wasteful. For most vaccines, there is a lack of supportive experimental data documenting a need for annual vaccination. When developing a vaccination protocol for a specific patient, choices should be made to select vaccines against diseases for which the patient is at risk and that produce protective immunity.Immune Response to Vaccination
The type of immune response that protects an animal against infectious diseases varies between pathogens and depends upon the route of introduction and site of replication of those pathogens. Protection may result from the presence of circulating immunoglobulins (humoral immunity), sensitized T-lymphocytes (cell-mediated immunity), immunoglobulins on mucosal surfaces, or a combination of these factors. Humoral immunity is important for protection against extracellular phases of systemic viral and bacterial infections and for protection against endotoxin and exotoxin induced diseases. Cell-mediated immunity is important in combating intracellular bacterial or viral infections, fungal disease, and protozoal disease. The non-specific immune system (phagocytic cells such as granulocytes and macrophages, natural killer cells, and complement) assists the humoral and cell-mediated immune systems. The non-specific immune system is crucial in the initial control of infection and can respond almost immediately. This system is not directly affected by vaccination or previous exposure to an infectious agent.
After the first exposure to an antigen, the cell-mediated system requires 6 days and the humoral system requires 14 days to reach optimum function. If the initial exposure results in memory cell creation, on subsequent exposures to this same antigen, the response of the immune system is rapid. This anamnestic response is the protective principle on which immunization is based. Although optimum immune system function may take 14 days following initial exposure, beneficial responses can help protect patients in the face of infection.
The immune response can be further categorized according to the location where it occurs: systemic and mucosal. Parenterally injected antigens usually result in a systemic immune response, whereas antigens transferred across a mucosal surface induce mucosal, and in some cases systemic, immunity. Most of the antibody classes responsible for systemic humoral immunity as well as the white blood cells responsible for cell-mediated immunity are not found on mucosal surfaces. Whether parenteral or local immunization is important for protection depends on the pathogenesis of the disease. Mucosal immunity can be particularly beneficial when the route of exposure of the pathogen is the same as the target tissue. The use of intranasal vaccines for upper respiratory infections is an example of local mucosal immune stimulation. The intranasal route has the advantage of stimulating systemic immunity as well as local antibody and cell-mediated immunity in the respiratory tract. It also does this more rapidly than parenterally administered vaccines.
Providing effective immunoprophylaxis for the patient population as a whole does not require that all cats presented for vaccination be inoculated with each antigen for which there is a vaccine currently licensed. Factors related to the individual patient, as well as factors unique to the infectious agent, should be taken into consideration when designing a vaccination protocol for an individual cat.
The clinician's assessment of the individual cat's RISK PROFILE takes into consideration information about: 1) the patient, 2) the patient's environment, and 3) the infectious agent.
Patient: Age at the time of exposure to an infectious agent is important in assessing an individual's risk. Although no age group can be considered entirely free from risk, kittens (less than 6 months of age) are generally more susceptible to infection than adult cats following exposure and therefore, represent the principal target population for feline vaccination protocols.
The presence of maternal antibody is an intrinsic host factor known to protect kittens following exposure to an infectious agent. Ironically, maternal antibody represents a significant risk factor because of possible neutralization of vaccine. Failure to vaccinate kittens after maternal antibody has declined sufficiently (approximately 12 weeks of age for FPV and earlier for FHV-1 and FCV) will increase the risk of infection. This is the single most common cause of vaccination failure in cats.
Patient's Environment: Population density and opportunity for exposure to other cats (free-roaming or "indoor-outdoor" activity) are among the most critical issues affecting the risk of exposure to an infectious agent. Cats and kittens living within multiple cat households and cluster populations (boarding, breeding or shelter facilities) are likely to have a substantially higher risk of infection than are cats living in 1 or 2 cat households. Furthermore, the introduction of new cats into a household/cluster poses a potential risk to the entire population.
Geographic distribution of various infectious agents may represent significantly different exposure risk to cats living in different areas. Periodic housing in boarding facilities also places cats at increased risk of exposure. In multiple cat households, sustained high ambient temperatures and humidity, in addition to a housing environment with less than 12 air exchanges per hour, increases the risk of exposure to respiratory pathogens.
Cats are at greater risk of exposure to FHV-1 and FCV if they are periodically housed in boarding, breeding or shelter facilities. These cats may benefit from booster vaccination against FHV-1 and FCV administered prior to exposure at intervals more frequent than every three years. Cats at risk of exposure to FeLV include outdoor cats, indoor/outdoor cats, stray cats, feral cats, open multi-cat households, FeLV-positive households, and households with unknown FeLV status. Cats in these situations should be vaccinated against FeLV annually.
Infectious Agent: Independent agent-associated variables, such as virulence, challenge dose, environmental stability, and mutation do influence the outcome of infection but can be difficult to objectively assess.
When assessing an individual's risk, these factors should be considered to determine how often to use CORE vaccines and which NON-CORE vaccines may be appropriate. Vaccines designated as CORE are recommended for administration to all cats based on the criteria that: 1) the consequences of infection are particularly severe (e.g., feline panleukopenia), 2) the infection in cats poses significant zoonotic potential (e.g., rabies), 3) the disease is prevalent and easily transmitted so that it poses a significant risk to the population of cats at large (e.g., feline herpesvirus and calicivirus), and 4) the vaccine selected is safe and efficacious.
The decision to vaccinate a cat with a vaccine that is NON-CORE should be based on the realistic evaluation of all the risk factors, as well as vaccine efficacy and safety.
Veterinarians can determine which type of vaccine should be used for a particular patient by understanding the differing characteristics of available products. The current choices are between modified-live vaccines (MLV), killed vaccines (KV), and subunit vaccines. Vaccines also differ in the route by which they are administered (parenteral or intranasal) and the number of antigen types they contain (monovalent or multivalent).
MLV vaccines must replicate within the patient in order to provide protective immunity. They are thought to have increased efficacy with better stimulation of cell-mediated immunity. MLV vaccines may also offer quicker protection in the face of an outbreak. Protective immunity can occur after 1 dose of most, but not all, MLV vaccines, whereas 2 doses are needed for most KV vaccines. There is decreased risk of certain serious adverse hypersensitivity reaction with MLV products as compared to KV vaccines. However, MLV vaccines can cause infectious disease in certain individuals and can be shed into the environment leading to infection and disease in cats in contact with vaccinated animals.
KV vaccines do not replicate, cannot cause infectious disease, nor shed to the environment. Adjuvants are normally added to KV vaccines to help stimulate protective immunity. Due to the larger antigenic mass and adjuvant systems normally found in KV vaccines, they have a greater tendency to stimulate fever and lethargy in the immediate post vaccination period than do MLV's. It is speculated that adjuvants may trigger immune-mediated events, including immediate hypersensitivity reactions and other adverse reactions in genetically predisposed individuals. In most cases, a minimum of 2 doses of KV vaccine must be administered to provide protective immunity.
Subunit and vectored vaccines are new varieties of vaccine types introduced through advancements in genetic engineering. Recombinant technology, the process of either deleting pathogenic genes from immunogenic organisms (bacteria or viruses) or inserting immunogenic genes into non-pathogenic carriers (vectors), is already being used to produce vaccines for the companion animal market. Genetically engineered viruses can be used to make either infectious or non-infectious vaccines. A principal goal in developing recombinant vaccines is to create vaccines with greater efficacy and safety. However, unique efficacy and safety issues can arise when vaccines are produced in this manner. As additional information becomes available on these products, veterinarians are encouraged to learn more about these vaccines and their role in clinical practice.
Table 1: Characteristics of vaccines currently available for use in cats
Vaccine type |
||
Characteristic |
Modified-live virus | Killed-virus |
| Route of Administration | Parenteral or local | Parenteral |
| Amount of Antigen per dose | Low | Moderate to high |
| Relative cost | Low | Moderate |
| Number of doses needed | 1 (1) | Multiple (2) |
| Includes an adjuvant | No | Yes (3) |
| Reversion to virulence | Possible | Not Possible |
| Potential for contamination (4) | Moderate | Low or none |
| Adverse Responses | Yes (5) | Yes (5) |
Notes: 1. Some live vaccines will require a second dose. 2. Some killed vaccines require only one initial dose. 3. Some killed vaccines do not use adjuvants. 4. This is the potential for a vaccine to become contaminated with a virulent adventitious agent during the manufacturing process. 5. All vaccines are associated with adverse responses.
Multiple Antigen (Combination) Vaccines
The decision to use multivalent or monovalent vaccines is not simple. The use of multi-antigen products can be convenient to owners and veterinarians alike, resulting in fewer injections for the patient. For a multiple antigen vaccine to be approved, its manufacturer must demonstrate that the multiple antigen vaccine produces the same level of immune response as the single antigen product. Therefore, the effectiveness of multiple antigen vaccine should be clinically indistinguishable from single antigen products. There is controversy about safety advantages or disadvantages between these types of products. The simultaneous use of several single antigen products tends to expose patients to higher amounts of proteins and, in certain cases, adjuvants as compared to the same antigens administered in a single dose multiple antigen approved vaccine. Therefore, there is speculation that there may be a safety advantage with the use of combination products. However, the rate of adverse responses appears to increase with concurrent administration of multiple antigens, whether administered as concurrent monovalent or as multivalent vaccines. There is an absence of credible observational data to lead the panel to a make a definitive recommendation.
Routes of Vaccine Administration
Currently and historically the majority of vaccines in companion animal practice are administered parenterally. The use of vaccination routes other than by injection should be considered in diseases for which a vaccine alternative is approved. Intranasal vaccines may be more effective for diseases in which there is protection at the primary site of replication, e.g., local protection of the respiratory tract against feline viral rhinotracheitis and calicivirus. Intranasal administration has the advantage of inducing local antibody and cell-mediated immunity in the respiratory tract, in addition to inducing systemic immunity. Another advantage of non-injected vaccine administration is the expectation that vaccine given in this manner would not be associated with sarcoma development. In the absence of any observational data, this advantage is speculative. On the other hand, intranasal vaccines tend to have a higher rate of post-vaccination side effects such as conjunctivitis, sneezing and shedding of vaccine virus. Therefore, the potential advantages of this route of administration must be balanced against the potential to do harm. KV vaccines are rarely effective when given by the intranasal route.
MLV herpes and calici vaccines approved for parenteral administration contain FCV and FHV-1 viruses that are attenuated for that route. If these vaccines are inadvertently administered to mucosal surfaces of the eyes, nose, or mouth, significant respiratory disease may develop. This inadvertent exposure may result from residual vaccine on the hair coat after vaccination or spilled vaccine on a surface that is accessible to the cat.
Vaccine efficacy can be determined in a controlled challenge-model experiment as required by USDA. The two most common procedures involve determining levels of circulating antibody and watching for signs of disease subsequent to challenge with pathogenic organisms. Antibody determinations are simple, inexpensive, and normally do not compromise an animal's welfare. Antibody levels assess B-lymphocyte and plasma cell responses against antigens. While antibody levels do not directly measure other cell-mediated immune responses, the presence of antibody indirectly suggests intact T-lymphocyte responses since antibody production is maximized by interaction between B- and T-lymphocytes. With some disease, antibody levels do not always correlate with protection. Therefore, vaccine efficacy is best determined by measuring signs of disease subsequent to challenge. These studies are complex, expensive, and seriously impact the welfare of the test animals.
For many diseases, vaccine efficacy is not a measure of absolute prevention of all clinical signs, but only the prevention of the most serious signs of disease. This does not mean that the vaccines are not worthy of use. Reduction in serious disease can be very important to patients and clients. Reductions in the amount of shed pathogens can significantly limit the seriousness of a disease outbreak in a population. This demonstrates the need to precisely understand a vaccine's efficacy for each component. Neither veterinarians, nor clients, should have unrealistic expectations concerning a vaccine's ability to prevent all signs of disease.