The Use of Vaccines



The Use of Vaccines



Although the principles of vaccination have been known for many years, vaccines and vaccination procedures are continuously evolving as we seek to improve both efficacy and safety. The earliest veterinary vaccines were often of limited efficacy and induced severe adverse effects, although these effects were considered acceptable when measured against the risks of acquiring disease. The vaccination protocols developed at that time reflected the inadequacies of these vaccines. Ongoing developments in vaccine design and production have resulted in great improvements in both vaccine safety and effectiveness. These improvements have permitted a reassessment of the relative risks and benefits of vaccination and have resulted in changes in vaccination protocols. Vaccination is not always an innocuous procedure. For this reason, the use of any vaccine should be accompanied by a risk-to-benefit analysis conducted by the veterinarian in consultation with the animal’s owner. Vaccination protocols should be customized to each animal, giving due consideration to the seriousness of the disease, the zoonotic potential of the agent, the animal’s exposure risk, and any legal requirements relating to vaccination.


The two major factors that determine vaccine use are safety and efficacy. We must always be sure that the risks of vaccination do not exceed those associated with the chance of contracting the disease. Thus it may be inappropriate to use a vaccine against a disease that is rare, is readily treated by other means, or is of little clinical significance. In addition, because the detection of antibodies is a common diagnostic procedure, unnecessary use of vaccines may complicate diagnosis based on serology and perhaps make eradication of a disease impossible. The decision to use vaccines for the control of any disease must be based not only on the degree of risk associated with the disease but also on the availability of superior control or treatment procedures.


The second major consideration is vaccine efficacy. Vaccines may not always be effective. In some diseases, such as equine infectious anemia, Aleutian disease in mink, and African swine fever, poor or no protective immunity can be induced even with the best vaccines. In other diseases, such as foot-and-mouth disease in pigs, the immune response is transient and relatively ineffective, and successful vaccination is difficult to achieve.


As a result of these considerations, some investigators have recommended that animal vaccines be divided into categories based on their importance. The first category consists of essential (or core) vaccines—those that are required because they protect against common, dangerous diseases and because a failure to use them would place an animal at significant risk of disease or death. Which vaccines are considered essential may vary based on local conditions and disease threats. The second category consists of optional (or noncore) vaccines. These are directed against diseases for which the risks associated with not vaccinating may be low. In many cases, risks from these diseases are determined by the location or lifestyle of an animal. The use of these optional vaccines would be determined by a veterinarian on the basis of exposure risk. A third category consists of vaccines that may have no application in routine vaccination but may be used under very special circumstances. These are vaccines directed against diseases of little clinical significance or vaccines whose risks do not significantly outweigh their benefits. Of course, all vaccine use should be conducted on the basis of informed consent. An animal’s owner should be made aware of the risks and benefits involved before seeking approval to vaccinate.


When vaccines are used to control disease in a population of animals rather than in individuals, the concept of herd immunity should also be considered. This herd immunity is the resistance of an entire group of animals to a disease as a result of the presence, in that group, of a proportion of immune animals. Herd immunity reduces the probability of a susceptible animal meeting an infected one so that the spread of disease is slowed or terminated. If it is acceptable to lose individual animals from disease while preventing epizootics, it may be possible to do this by vaccinating only a proportion of the population.



Administration of Vaccines


Most vaccines are administered by injection. All such vaccines should be injected carefully and with due regard to the anatomy of the animal. Care must be taken not to injure or introduce infection into any animal. All needles used must be clean and sharp. Dirty or dull needles can cause tissue damage and infection at the injection site. The skin at the injection site must be clean and dry, although excessive use of alcohol swabbing should be avoided. Vaccines are provided in a standard dose, and this dose should not be divided to account for an animal’s size. Doses are not formulated to account for body weight or age. There must be a sufficient amount of an antigen to trigger the cells of the immune system and provoke an immune response. This amount is not related to body size. (Unfortunately, the risk of an adverse event occurring is increased in the smallest animals, so it may be necessary to make some adjustment in vaccine dose for safety reasons.) Vaccination by subcutaneous or intramuscular injection is the simplest and most common method of vaccine administration. This approach is obviously excellent for small numbers of animals and for diseases in which systemic immunity is important. In some diseases, however, systemic immunity is not as important as local immunity, and it is perhaps more appropriate to administer the vaccine at the site of potential invasions. Therefore, intranasal vaccines are available for infectious bovine rhinotracheitis of cattle; for Streptococcus equi infections in horses; for feline rhinotracheitis, Bordetella bronchiseptica, coronavirus, and calicivirus infections; for canine parainfluenza and Bordetella infection; and for infectious bronchitis and Newcastle disease in poultry. Unfortunately, these methods of administration require that each animal be dealt with on an individual basis. When animal numbers are large, other methods must be employed. For example, aerosolization of vaccines enables them to be inhaled by all the animals in a group. This technique is employed in vaccinating against canine distemper and mink enteritis on mink ranches and against Newcastle disease in poultry. Alternatively, the vaccine may be put in the feed or drinking water, as is done with Erysipelothrix rhusiopathiae vaccines in pigs and against Newcastle disease, infectious laryngotracheitis, and avian encephalomyelitis in poultry. Alternative routes of vaccine administration that are in development or employed in humans include liquid-jet injectors, microinjection, and topical skin application.


Vaccination is now the most important method of preventing infectious diseases in farmed fish. Most commercial fish vaccines consist of inactivated products that are administered either by intraperitoneal injection or, preferably, by immersing the fish in a dilute antigen solution. Immersion results in the antigen being deposited on mucosal surfaces such as the gills or oral cavity, and some may be swallowed.



Multiple-Antigen Vaccines


For convenience, it has become common to employ mixtures of organisms within single vaccines. For respiratory diseases of cattle, for example, vaccines are available that contain infectious bovine rhinotracheitis (BHV-1), bovine virus diarrhea (BVDV), parainfluenza 3 (P13), and even Mannheimia hemolytica. Dogs may be given vaccines containing all of the following organisms: canine distemper virus, canine adenovirus 1, canine adenovirus 2, canine parvovirus 2, canine parainfluenza virus, leptospira bacterin, and rabies vaccine. These mixtures may be used when exact diagnosis is not possible and may protect animals against several infectious agents with economy of effort. However, it can also be wasteful to use vaccines against organisms that may not be causing problems. When different antigens in a mixture are inoculated simultaneously, competition occurs between antigens. Manufacturers of multiple-antigen vaccines take this into account and modify their mixtures accordingly. Vaccines should never be mixed indiscriminately since one component may dominate the mixture or interfere with the response to the other components.


Some veterinarians have questioned whether the use of complex vaccine mixtures leads to less than satisfactory protection or increases the risk for adverse side effects. They are concerned that the use of 5- or 7-component vaccines in their pets will somehow overwhelm the immune system, forgetting that we and our animals encounter hundreds of different antigens in daily living. The suggestion that these multiple-antigen vaccines can overload the immune system is unfounded, nor is there any evidence to support the contention that the risk for adverse effects increases disproportionately when more components are added to vaccines. The success of a 23-component pneumococcal vaccine in AIDS patients should serve as a reassurance that multiple component vaccines are not overwhelming. Certainly such vaccines should be tested to ensure that all components induce a satisfactory response. Licensed vaccines provided by a reputable manufacturer will generally provide satisfactory protection against all components.



Vaccination Schedules


Although it is not possible to give exact schedules for all veterinary vaccines available, certain principles are common to all methods of active immunization. Most vaccines require an initial series in which protective immunity is initiated, followed by revaccination (booster shots) at intervals to ensure that this protective immunity remains at an adequate level.



Initial Series


Because maternal antibodies passively protect newborn animals, it is not usually possible to successfully vaccinate animals very early in life. If stimulation of immunity is deemed necessary at this stage, the mother may be vaccinated during the later stages of pregnancy, the vaccinations being timed so that peak antibody levels are achieved at the time of colostrum formation. Once an animal is born, successful active immunization is effective only after passive immunity has waned. Since it is impossible to predict the exact time of loss of maternal immunity, the initial vaccination series will generally require administration of multiple doses. Current guidelines for essential canine and feline vaccines, for example, indicate that the first dose of vaccine should be administered at 8 weeks of age, followed by a second dose 3 to 4 weeks later, and concluding at about 15 weeks of age. (These are not, strictly speaking, booster doses. They are simply designed to trigger a primary response as soon as possible after maternal immunity has waned.) All animals should then receive a booster dose 12 months later. Administration of vaccines to young animals is discussed in Chapter 21.


The timing of initial vaccinations may also be determined by the disease. Some diseases are seasonal, and vaccines may be given before disease outbreaks are expected. Examples of these include the vaccine against the lungworm Dictyocaulus viviparus given in early summer just before the anticipated lungworm season, the vaccine against anthrax given in spring, and the vaccine against Clostridium chauvoei given to sheep before turning them out to pasture. Bluetongue of lambs is spread by midges (Culicoides variipennis) and is thus a disease of midsummer and early fall. Vaccination in spring will therefore protect lambs during the susceptible period.



Revaccination and Duration of Immunity


As pointed out in Chapter 18, the phenomenon of immunological memory is not well understood; yet it is the persistence of memory cells, B cells, plasma cells, and T cells after vaccination that provides an animal with long-term protection. The presence of long-lived plasma cells is associated with persistent antibody production so that a vaccinated animal may have antibodies in its bloodstream for many years after exposure to a vaccine. It is believed that these long-lived plasma cells are stimulated to survive by activation with microbial PAMPs acting through TLRs and that it is the antibodies that are mainly responsible for long-term protection.


Revaccination schedules depend on the duration of effective protection (Table 24-1). This in turn depends on specific antigen content, whether the vaccine consists of living or dead organisms, and its route of administration. In the past, relatively poor vaccines may have required frequent administration, perhaps as often as every 6 months, to maintain an acceptable level of immunity. Newer, modern vaccines usually produce a long-lasting protection, especially in companion animals; many require revaccination only every 3 years, whereas for others, immunity may persist for an animal’s lifetime. Even killed viral vaccines may protect individual animals against disease for many years. Unfortunately, the minimal duration of immunity has, until recently, rarely been measured, and reliable figures are not available for many vaccines. Likewise, although serum antibodies can be monitored in vaccinated animals, tests have not been standardized, and there is no consensus regarding the interpretation of these antibody titers. Even animals that lack detectable antibodies may well have significant resistance to disease. Nor is there much information available regarding long-term immunity on mucosal surfaces. In general, immunity against feline panleukopenia, canine distemper, canine parvovirus, and canine adenovirus is considered to be relatively long-lasting (>5 years). On the other hand, immunity to feline rhinotracheitis, feline calicivirus, and Chlamydophila is believed to be relatively short. One problem in making these statements is variability among individual animals and among different types of vaccine. Thus recombinant canine distemper vaccines may induce immunity of much shorter duration than conventional, modified live vaccines. There may be a great difference between the shortest and longest duration of immunological memory within a group of animals. Duration of immunity studies are confounded by the fact that in many cases older animals show increased innate resistance. Different vaccines within a category may differ significantly in their composition, and although all vaccines may induce immunity in the short term, it cannot be assumed that all confer long-term immunity. Manufacturers use different master seeds and different methods of antigen preparation. The level of immunity required for most of these diseases is unknown. A significant difference exists between the minimal level of immunity required to protect most animals and the level of immunity required to ensure protection of all animals.



Annual revaccination has been the rule for most animal vaccines since this approach is administratively simple and has the advantage of ensuring that an animal is regularly seen by a veterinarian. It is clear, however, that vaccines such as those against canine distemper or feline herpesvirus induce protective immunity that can last for many years and that annual revaccination using these vaccines is unnecessary. A growing body of evidence now indicates that most modified live viral (MLV) vaccines induce lifelong sterile immunity in dogs and cats. In contrast, immunity to bacteria is of much shorter duration and often may prevent disease but not infection. Old dogs and cats rarely die from vaccine-preventable disease, especially if they have been vaccinated as adults. Young animals, in contrast, may die from such diseases, especially if not vaccinated or if vaccinated at an incorrect age. A veterinarian should always assess the relative risks and benefits to an animal in determining the use of any vaccine and its frequency of administration. It may therefore be good practice to use serum antibody assays such as ELISAs, if available, to provide guidance on revaccination intervals. Persistent antibody titers may indicate protection, but this is not guaranteed, especially if cell-mediated immune mechanisms are important for protection. Likewise, animals with low or undetectable serum antibody levels may still be protected as a result of persistence of memory B and T cells capable of responding rapidly to reinfection.


Notwithstanding the previous discussion, animal owners should be made aware that protection against an infectious disease can only be maintained reliably when vaccines are used in accordance with the protocol approved by the vaccine-licensing authorities. The duration of immunity claimed by a vaccine manufacturer is the minimum duration of immunity that is supported by the data available at the time the vaccine license is approved. This must always be taken into account when discussing revaccination protocols with an owner.

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Jul 18, 2016 | Posted by in PHARMACOLOGY, TOXICOLOGY & THERAPEUTICS | Comments Off on The Use of Vaccines

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