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.

Maternal Antibodies

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.

Medications and Vaccines

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.