Nowadays, modern recombinant DNA technology provides the means for selective mutations with low-risk reversion frequency, making the reversion of modified-live vaccines to cause disease very unlikely and thus, inoculation much more safe and effective than earlier forms of these vaccines. However, because some live, attenuated viral components may be shed after immunization, it is recommended that dogs living in an environment with other dogs who are ill or immunosuppressed for reasons discussed above be administered killed vaccines and not modified-live vaccines to prevent possibility of infection in the immunocompromised dog.
Recently in clinical medicine, there is the realization that some forms of epileptic seizures may manifest as a direct effect of immunologic mechanisms. In some of these cases, vaccination may trigger these mechanisms because introduction of an antigen sets off an immune assault directed on the nervous system. Though a rare condition, in canine medicine, neurologic disease has been associated with use of modified-live canine distemper antigen. As is often the case with adverse reactions using modified-live vaccines, immunosuppression may also play a role in development of neurologic reactions. Similar to the actual disease process of canine distemper, when modified-live virus is introduced into the dog, if the immune system does not respond rapidly enough then attenuated virus can cross the blood-brain barrier or enter the cerebrospinal fluid and gain access to the central nervous system. Replication of the attenuated virus in the tissues of the brain, though not pathogenic, cause an inflammatory immune response in the brain tissue resulting in tissue damage and lesions that give rise to neurologic symptoms. Such symptoms, which can present several days to weeks following the vaccination, include motor weakness, incoordination, difficulty breathing and/or epileptic seizures and may be preceded 24-48 hours by fever, depression, nausea and vomiting. Dogs demonstrating neurologic disorders following vaccination may be immunosuppressed or more predisposed to immunosuppressive effects of polyvalent vaccines and, therefore, should be considered candidates for immunization with killed vaccines or monovalent vaccines when available.
The underlying pathologic changes that bring about Hypertophic Osteodystrophy (HOD; often called metaphyseal osteopathy in the research literature-- refer to "Growing Pains: Growth-Associated Bone Disorders in the Dog") are identical for both vaccine (or pathogen)-associated HOD and developmental/dietary-associated HOD. This was established by A.P. Mee and colleagues in a series of peer-reviewed publications. In fact, Mee's group, physicians using canine models to explore cellular mechanisms responsible for Paget's disease in humans, characterized the cellular mechanisms responsible for HOD. Mee's group provided considerable evidence that the defect in osteoclasts (increased number and size), which occur as the primary step in HOD development, occur as a result of increased levels of interleukin-6 (IL-6; a multi-functional cytokine produced by immune cells--macrophages, T-cells, B-cells--and endothelial cells).
Recent research exploring the cause for persistent arthritic symptoms in human patients previously diagnosed and treated for Lyme disease has linked recurrent arthritic symptoms to autoimmunity triggered by a protein carried by the Lyme disease organism, Borrelia burgdorferi. Put more simply, it has been found that some people have inherited a protein on their normal cells that is very similar to an antigen on the surface of the Lyme bacteria. When these people contract Lyme disease, their bodies launch an immune defense directed at the Lyme bacteria by targeting this particular antigen. As a result, their immune system will attack both the bacteria carrying this protein as well as their own normal cells that also carry this protein. Therefore, even after the infectious microorganisms are eradicated, symptoms of arthritis persist because the immune system continues to attack their own normal cells. This condition is known as "molecular mimicry," and these findings are of particular relevance to immunologists, especially to those who have developed vaccines against Lyme disease. Immune response derived from Lyme vaccines currently undergoing testing in clinical trials are directed at this protein antigen, therefore, it is anticipated that a small population of individuals may have a genetic predisposition for developing autoimmune symptoms after immunization with these vaccines. Interestingly, the observation that some dogs develop arthritic symptoms following vaccination with Lyme vaccine, despite the absence of clinical Lyme disease, suggests that an autoimmune reaction to the Lyme vaccine may develop in canines as well as humans. To date, however, "molecular mimicry" has not yet been demonstrated in the canine host.
Allergic reactions to vaccines are extremely rare; however, they may occur as a result of hypersensitivity to antibiotics or preservatives, or to an antigenic component of the vaccine, commonly the leptospirosis bacterin (see Canine Anaphylaxis). Allergic reactions to vaccines can result in mild symptoms of localized swelling to severe physiologic symptoms leading to systemic shock and eventually death. Recent clinical findings suggest that cases of severe anaphylaxis may be a result of underlying endocrine disorders. The endocrine system is composed of glands that control the secretion of hormones involved in a number of normal bodily functions including the regulation of immune response. Certain hormones are synthesized by the endocrine glands in response to immune factors and act as a negative feedback to control and balance the immune reaction. In particular, glucocorticoids, such as cortisol, which are produced by the adrenal glands are hormones which through a number of pathways regulate and suppress the function of B cells, T cells, macrophages and other mediators of inflammation as well as controlling a number of other physiological processes including electrolyte balance. However, although uncommon, some dogs may have an underlying disorder of the adrenal glands that causes a condition referred to as hypoadrenocorticism (Addison's disease) which precludes the ability of the adrenal glands to secrete glucocorticoids in response to various stress stimuli including immunization. As a result, deficiency of glucocorticoids in response to immunization can result in symptoms of lethargy, loss of appetite, weakness, vomiting, diarrhea, seizures and in more severe cases leads to life-threatening systemic shock known as Addisonian crisis. Hypoadrenocortism is more common in females than males and usually presents in dogs between 1 and 7 years of age. Evidence suggests a genetic predisposition to the development of this disorder particularly in Standard Poodles, Labrador retrievers and Portuguese water spaniels. Although some dogs may present with symptoms indicative of disease (depression, generalized weakness, dehydration), many cases remain subclinical and are only diagnosed after hypoadrenal crisis precipitated by physical stress associated with trauma, infections, surgery, or immunization. Because symptoms of adrenal insufficiency are similar to adverse systemic reactions resulting from allergic anaphylaxis, dogs which have exhibited severe adverse reaction to immunization should be tested for this endocrine disorder. The adrenocorticotrophic hormone (ACTH) stimulation test is currently the method for clinical diagnosis.
Use of both modified-live vaccines and killed vaccines are contraindicated for immunization of pregnant bitches unless the vaccine has been specifically approved for this purpose or risk of contracting an infectious disease exceeds potential risks of vaccinating to the dam and litter. Problems associated with vaccination during pregnancy include fetal resorptions, spontaneous abortions, and birth defects. Advanced proper planning prior to the bitch's breeding cycle, which would include updating necessary inoculations, should exclude the necessity to vaccinate during pregnancy. Routine annual booster administration does not justify risks and should be postponed until the litter is whelped and the puppies are weaned (see Annual Boosters: How necessary are they? below).
Many times, failure of a vaccine to protect against a particular disease is blamed on the quality of the vaccine. However, vaccine ineffectiveness is most often a result in failure, whether knowingly or unknowingly, to follow the manufacture's recommendation for schedule, storage and administration. Some common factors influencing vaccine effectiveness include the following:
Since the incubation period of most infectious diseases is of shorter duration than the amount of time required for a vaccine to produce a sufficient antibody level required for protective immunity, vaccinating a dog shortly before, during or after it is exposed to an infectious disease will not protect the dog from contracting the disease. This is particularly critical during primary active immunization during which a dog is inoculated against a disease for the first time. In contrast, booster vaccines usually provide a rapid immune response and increase in protective antibodies.
Vaccines that are stored improperly or exposed to environmental extremes are at increased risk for inefficacy. Once lyophilized components of the vaccine are mixed with the accompanying vaccine diluent, the inoculant should be administered promptly and not stored for any length of time in the reconstituted form. Though many vaccines are distributed as two vials, a lyophilized component and a diluent component, which must be mixed together prior to injection, it is important to note that different vaccine brands or types should not be mixed together or administered with the same needle or syringe used to administer another vaccine. Doing so may cause an interaction of the vaccine components, which may inactivate particular antigens and prohibit proper immune response. Additionally, although killed vaccines are also susceptible to improper handling, careful handling of modified-live vaccines is critical because vaccine efficacy is dependent upon the ability of the modified viruses to replicate. Conditions that inactivate the viruses will lead to vaccine failure.
Another important factor influencing vaccine efficacy, and also safety in this case, is adhering to the route of administration recommended by the manufacturer. Today, most modified-live vaccines are approved for subcutaneous (beneath the skin) injection, however, to be effective, some vaccines still require special routes of administration. This is true of some modified-live rabies vaccines. Because the modified rabies viruses of some vaccines require nerve-tissue to replicate, these vaccines will only produce enough antigens sufficient to induce an immune response if injected into muscle (intramuscular administration). In some cases, killed vaccines also require a special route of administration. Vaccines such as those for protection against kennel cough stimulate local mucosal immunity against the disease in the respiratory tract and require intranasal administration. Furthermore, administration of some killed vaccines by a route other than directed may lead to severe systemic reactions since many of these vaccines contain adjuvant, or helper, components such as aluminum hydroxide which enhance the immune response to the killed antigen. Subcutaneous injections of such vaccines can lead to localized tissue damage or to severe systemic allergic reactions.
Occassionally, despite being immunized, a puppy between the ages of 4 months and 1 year will contract one of the diseases for which it has been previously vaccinated. Usually, the vaccine will be blamed, however, in such a case the cause for vaccine inefficacy usually lies elsewhere.
One of the most critical aspects of immunity, but perhaps the most often responsible for vaccine failure, is passive immunity acquired by a puppy when it ingests colostrum in the dam's milk during the first few days following birth. Colostrum, which is rich in maternal antibodies, is essential for protection against infection and survival of the puppies during the first several weeks following birth when their own immune systems are not yet developed. However, in addition to protecting the puppy from infection, maternal antibodies also have the ability to interfere with active immunization by binding to and neutralizing antigen components in vaccines before the puppy's immune system can launch its own response. Since the passive immunity acquired from maternal antibodies is not permanent and diminishes over time, eventually, passive immunity will diminish and because of maternal antibody interference, weak, if any, active immunity will have developed to protect the puppy from subsequent infections. For this reason, multiple vaccine schedules have been designed to increase active immunity in the face of diminishing maternal antibody concentrations with, ideally, the last booster vaccine administered after total depletion of maternal antibody to ensure complete active immunization.
In light of this, an increased risk for vaccine failure may occur for schedules which prematurely discontinue the booster administration. Because many factors such as level of maternal immunity, amount of colostrum produced, antibody content of the colostrum, or amount of colostrum ingested and absorbed can greatly influence levels and persistence of maternal antibody in any one individual puppy, optimum time for booster vaccines will vary from individual to individual. Because it is neither cost- nor time- effective to determine serum maternal antibody levels for each puppy, booster vaccine schedules are generalized with timing of booster administration intended to ensure protective immunization in animals demonstrating either early or late maternal antibody depletion. However, it was discovered that of the puppies vaccinated using the initial schedules which required a final vaccine administration at 16 weeks of age, more than 20% were still found to have circulating maternal antibodies as late as 18 weeks that could potentially interfere with complete protection. Therefore, a new schedule was suggested recommending that a final booster be administered between 20 and 22 weeks of age to decrease risks associated with incomplete immunization.
In further support of extended puppy booster schedules are the conclusions of a recent clinical study examining the efficacy of various brands of vaccines for promoting active immunization and disease protection in puppies. It was found that some brands of vaccines are less efficient than others at inducing protective immunity when administered to puppies between 9 to 16 weeks of age. Because ability for the vaccine to promote protective immunity increased as a factor of puppy age, vaccines that produced lower immune responses are probably more susceptible to maternal antibody interference.
Occassionally, outbreaks of canine parvo virus cause severe disease in litters between 6 and 14 weeks of age. Puppies within this age period are particularly vulnerable to contracting disease because during this time, levels of maternal antibodies may still be high enough to prevent active immunization but too low to fight off the infection. Therefore, most puppy vaccine schedules recommend administration of booster vaccines at 2-3 weeks intervals.
Skin ailments associated with food or seasonal allergens are a common problem in canine medicine. Such allergies are widely treated with glucocorticosteroids, such as prednisone (or prednisolone), that inhibit the immune response and decrease inflammation and symptoms of itchy skin. Because such drugs are classified as immunosuppressive agents, administration of vaccines while a dog is receiving glucocorticosteroid treatment should be considered carefully. Though clinical research has found no evidence to suggest that use of glucocorticosteroids prevents effective immunization (since dogs vaccinated while receiving drug treatment were protected against infectious disease when later challenged), adverse vaccine reactions related to immunosuppression (as previously discussed) could present potential complications. To reduce possible adverse reactions of immunosuppression that may be associated with glucocorticosteroid treatment, dogs with seasonal allergies should be vaccinated during the symptom-free time of year when they are off medication. However, for some underlying health disorders, discontinuing glucocorticosteroid treatment during immunization may be dangerous. For example, in the case of dogs with adrenal insufficiency (discussed above), glucocorticosteroid dosage should be continued and may even need to be increased during the time of vaccination to prevent adrenal insufficiency crisis. Therefore, the decision to temporarily reduce or discontinue glucocorticosteroid treatment should be carefully assessed based on the underlying condition of each dog.
Another topic of controversy surrounding vaccination is the procedure of annual immunization. Although many veterinary clinics still recommend annual re-boostering to protect against disease, some others are now employing a three-year re-booster schedule (see Colorado State University's Veterinary School Vaccine Protocol) . This new schedule is based on the premise that active immunization to viral antigens may persist for years or perhaps even throughout the life of the dog and, therefore, provide long-lasting protection without the need for revaccination. However, it should be noted that many factors, some of which are discussed above, such as timing of primary immunization in regard to maternal antibody levels, efficacy of a particular vaccine to induce an immune response, use of killed versus modified-live vaccine and use of polyvalent versus monovalent vaccines, as well as immune-response of the individual dog at the time of inoculation may influence outcome effecting long-term protective immunity. Therefore, some dogs, particularly young adults who may not have developed complete immunity during their primary immunizations as puppies, may not be adequately protected against infectious disease if not administered an annual booster as an adult. To reduce this risk, three-year booster schedules should be employed only after a dog receives an annual booster as an adult dog, approximately one year following its primary immunization series as a puppy.
Though the general consensus among specialists in the field is that yearly vaccination against viral infections associated with canine distemper virus, canine parvovirus and canine adenovirus are generally unnecessary since active immunity induced by these vaccines provide at least several years of protection, this consensus, however, does not apply and should not be generalized to bacterin vaccines, which immunize against diseases associated with bacterial organisms. In fact, clinical evidence suggests that bacterin-derived vaccines including those which protect against Bordetella bronchiseptica (kennel cough), Leptospira (Leptospirosis), and Borrelia burgdoferi (Lyme disease) probably don't even provide protective immunity for 12 months suggesting that more frequent vaccination for these diseases are required. It is perhaps the common use of combination (all-in-one) vaccines containing bacterins, which immunize against bacterial infections such as Leptospirosis and/or kennel cough in addition to common viral infections, that gave rise to the practice of frequent vaccine administration. Indeed the incorrect generalization of long-term immunity, associated with vaccination against viral immunogens, to bacterin-based vaccines may lead to a decrease in annual vaccination for bacterial-based diseases and subsequently give rise to a resurgence of outbreaks of bacterial disease in the coming years. In light of this, annual re-boostering against bacterial diseases should continue despite discontinuation of yearly vaccination against viral diseases. For more information on bacterin vaccines, please refer to the following articles: