Although vaccine manufacturers produce high quality products, these will not be effective if administered by the wrong route, in the wrong dose, or at the wrong time. Thus careful and appropriate administration is required if maximum benefit is to be afforded by vaccination. One must not lose sight of the objectives of vaccination. Vaccines are given to protect animals against significant infectious diseases to which they have a risk of exposure. Vaccines should therefore only be given when these benefits are obvious and outweigh any possible adverse effects. Potential risks include adverse reactions, the likelihood of acquiring the disease, and the severity of the disease. On the other hand, benefits include protection from infection and death, reduction in disease severity, and any contribution to herd immunity. Vaccines should be administered no more frequently than necessary to confer protection. It is of course equally inappropriate to vaccinate animals in such a way that any immunity conferred is insufficient to protect them. Veterinarians assessing vaccine risk must also consider any benefits to human health that might result from protection against zoonotic infections. Since the 1990s, there has been a concerted effort to classify vaccines into those essential for animal health and thus mandatory (CORE vaccines) and those whose use depends upon specific risk assessment (nonCORE vaccines). That terminology is used here although it may be considered a false dichotomy. The use of every vaccine should be based on an objective and thorough risk assessment. The veterinarian must make their own professional judgment and an informed decision regarding vaccine use. Designation of core vaccines does not absolve them from their professional responsibilities in this respect. Veterinarians should only use effective vaccines licensed by their national authorities and the vaccines must be used in accordance with the label directions. They should not be used unless the veterinarian has either diagnosed a specific disease or is aware of its presence in an area, because otherwise it is not possible to determine the benefits and risks of vaccination. Certain principles are common to all methods of active immunization. Most vaccines require an initial series in which the immune system is primed and protective immunity initiated, followed by revaccination (booster shots) at intervals to ensure that this protective immunity remains at an adequate level. Because maternal antibodies passively protect newborn animals, it is not usually possible to vaccinate very young animals successfully. If protection is deemed necessary at this stage, the mother may be vaccinated during pregnancy. Maternal vaccinations should be 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 maternal antibodies have waned. Animals should be revaccinated 12 months later or at 1 year of age. It is unclear whether maternal antibodies can always block antibody responses to intranasal vaccines. Despite high levels of circulating maternal antibodies, maternal interference does not always occur and nasal antibody production is often unimpaired. The timing of initial vaccinations may also be determined by disease epidemiology. Some diseases are seasonal, and vaccines may be given before outbreaks are anticipated. 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 and is thus a disease of midsummer and early fall. Vaccination in spring will therefore protect lambs during the susceptible period. Similar considerations apply to mosquito-borne/wet season diseases. When deciding on the optimal interval between the first immunization and the booster shot it is important to consider how B cells and T cells differentiate. These cells respond rapidly to antigen and generate effector cells or plasma cells. Once this phase is over, most effector cells die while the survivors differentiate into memory cells. Memory T cells may take several weeks after the primary immune response to reach maximal numbers. Only when this memory phase develops can a significant secondary response be induced. As a general rule it is better to wait for as long as possible between prime and boost. Boosting too soon may well result in suboptimal secondary responses. (But boosting too late may open a window of vulnerability). Excessive boosting of mice appears to drive T cells toward terminal differentiation and deplete the population of central memory cells. Similar considerations apply to B cell responses. They need time to develop memory cells and premature boosting runs the risk of generating suboptimal memory. Computer modeling suggests that an interval of several weeks is necessary to obtain optimal secondary responses. In children, 4 to 8 weeks is considered to be the minimal interval between the first two doses by the Centers for Disease Control and Prevention (CDC), whereas six months is the recommended interval between the second and third vaccine doses. Studies on revaccination with Clostridial vaccines in sheep also suggest that an interval of 8 weeks between vaccine doses is optimal. A study on boosting cattle with rabies vaccine suggested that the optimal response was obtained with a 180-day interval between vaccine doses. Although experimental data suggest that vaccination intervals be somewhat longer than currently recommended, one must also remember that it is essential not to leave a window of susceptibility between vaccine doses. For practical purposes, it is generally recommended that in dogs and cats the minimal interval should be 2 to 3 weeks. For larger animals such as horses it is generally a minimum of 3 to 4 weeks. In general, the longer the interval between booster shots, the better it is for the induction of a maximal protective response. Decisions on vaccination frequency however must be at the discretion of the vaccinating veterinarian. It is the persistence of memory 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. Revaccination schedules depend on the duration of effective protection. 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 six months, to maintain an acceptable level of immunity. Modern vaccines usually produce a long-lasting protection, especially in companion animals. Many require revaccination only every three or four years, whereas for others, immunity may persist for an animal’s lifetime. Even inactivated viral vaccines may protect individual animals against disease for many years. Unfortunately, the minimal duration of immunity has rarely been measured, until recently, and reliable figures are not available for many vaccines. 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 have significant cell-mediated resistance to disease. Nor is there much detailed 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 herpesvirus, feline calicivirus, and Chlamydia is believed to be relatively short. One problem in making these statements is the variability among individual animals and among different types and brands of vaccine. Thus recombinant canine distemper vaccines may induce shorter duration immunity 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 many older animals have increased innate resistance. Different vaccines within a category may differ significantly in their performance, 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. 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 was once the rule for most animal vaccines because this approach was administratively simple and had the advantage of ensuring that an animal was seen regularly by a veterinarian. It is clear, however, that modern 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 excessive. A growing body of evidence now indicates that most modified live viral 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. In contrast, young animals die from such diseases, especially if not vaccinated or vaccinated prematurely. A veterinarian should always assess the relative risks and benefits to an animal in determining the timing of any vaccination. It is therefore be good practice to use serum antibody assays such as rapid test ELISAs (enzyme-linked immunosorbent assays) or lateral flow assays, if available, to provide guidance on revaccination intervals. Persistent antibody titers determine whether an animal requires additional protection. These tests not only identify those animals that have responded to vaccination, they can determine if an animal is a nonresponder. They can determine if an animal that previously suffered from an adverse event really requires revaccination. They can determine whether an animal with an undocumented vaccine history needs to be vaccinated and with which vaccines. They can determine which animals in a shelter undergoing a disease outbreak are susceptible and so require vaccination. They can also determine whether revaccination is really necessary at three years. It should be pointed out, however, that 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. “Blind” revaccination should be avoided if appropriate serum antibody assays are available. Notwithstanding this 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. Mothers transfer antibodies to their offspring through feeding colostrum in most domestic mammals (Fig. 8.1). Once absorbed from the intestine, these maternal antibodies inhibit neonatal antibody synthesis by acting through regulatory pathways that ensure that the body does not make more antibodies than it needs. They inhibit B cells, not T cells. As a result, they prevent the successful vaccination of very young animals. This inhibition may persist for many months. Its duration depends primarily on the amount (titer) of antibodies transferred and the half-life of the immunoglobulins involved. This problem can be illustrated using the example of vaccination of puppies against canine distemper. Maternal antibodies, absorbed from the puppy’s intestine, reach maximal levels in serum by 12 to 24 hours after birth. These levels then decline slowly through normal protein catabolism. The catabolic rate of proteins is exponential and is expressed as a half-life. The half-life of specific antibodies against distemper and canine infectious hepatitis is 8.4 days. Experience has shown that, on average, the level of maternal antibodies to distemper in puppies declines to insignificant levels by about 10 to 12 weeks, but this may range from 6 to 16 weeks. (The titer of maternal antibodies, not the animal’s age is the determining factor.) In a population of puppies, the proportion of susceptible animals therefore increases gradually from a very few or none at birth, to most puppies at 10 to 12 weeks. Consequently, very few newborn puppies can be successfully vaccinated, but most can be protected by 10 to 12 weeks. Rarely, a puppy may reach 15 or 16 weeks before it can be successfully vaccinated. If virus diseases were not so common, it would be sufficient to delay vaccination until all puppies were about 12 weeks old, when success could be almost guaranteed. In practice however, a delay of this type means that an increasing proportion of puppies, fully susceptible to disease, would be without immune protection—an unacceptable situation. Nor is it feasible to vaccinate all puppies repeatedly at short intervals from birth to 12 weeks, a procedure that would also ensure almost complete protection. Therefore a compromise must be reached. The earliest recommended age to begin vaccinating a puppy or kitten with a reasonable expectation of success is at six weeks. Colostrum-deprived orphan pups lacking maternal antibodies, may be vaccinated at two weeks of age. Because it is impossible to predict the exact time of loss of specific maternal antibodies, any initial vaccination series will generally require administration of at least three doses. Current guidelines for essential canine and feline vaccines, for example, indicate that the first dose of vaccine should be administered as early as 6 to 8 weeks of age, and revaccinated at 2 to 4 week intervals until they are about 16 weeks of age. Strictly speaking these are not booster doses. They are simply designed to trigger a primary response as soon as possible after maternal antibodies have declined. Rabies is a core vaccine that should be given at 14 to 16 weeks. In kittens the half-life of maternal antibodies to feline panleukopenia is 9.5 days. The appropriate protocol would be to use three doses of the core vaccines (herpesvirus, calicivirus, and panleukopenia) at 8 to 9 weeks, 3 to 4 weeks later, and at 14 to 16 weeks; feline leukemia vaccine can be given at 8 weeks and 3 to 4 weeks later; and rabies vaccine can be given at 8 to 12 weeks, depending on the type of vaccine used (Fig. 8.2). Similar considerations apply when vaccinating large farm animals (Fig. 8.3). The prime factor influencing the duration of maternal immunity is the level of antibodies in the mother’s colostrum. In foals, maternal antibodies to tetanus toxin can persist for six months and antibodies to equine arteritis virus for as long as eight months. Antibodies to bovine viral diarrhea virus may persist for up to nine months in calves. The half-lives of maternal antibodies against equine influenza and equine arteritis virus antigens in the foal are 32 to 39 days respectively. As in puppies, a young foal may have nonprotective levels of maternal antibodies long before it can be vaccinated. Maternal antibodies, even at low titers, effectively block immune responses in young foals and calves, so premature vaccination may also be ineffective. The effective response to vaccines increases progressively after the first six months of life. A safe rule is that calves and foals should be vaccinated no earlier than three to four months of age, followed by one or two revaccinations at four-week intervals. The precise schedule will depend on the vaccine used and the species to be vaccinated. Animals vaccinated before six months of age should always be revaccinated at six months or after weaning, to ensure protection.
The administration of vaccines
Vaccination principles
Vaccination schedules
Initial series
Vaccination intervals
Revaccination
Maternal immunity
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