There are many reasons why vaccination may fail. In some cases, the vaccine may not be effective because it contains strains of organisms or antigens different from the disease-producing agent. In other cases, the method of manufacture may have destroyed the protective epitopes, or there may simply be insufficient antigen. Such problems are uncommon and can be avoided by using vaccines from reputable manufacturers. More commonly, an effective vaccine may fail due to unsatisfactory administration or storage. For example, a live bacterial vaccine may lose potency as a result of use of antibiotics. Route of administration may also affect efficacy. When vaccine is administered to poultry or mink by spraying or in drinking water, the spray may not be evenly distributed throughout a building, or some animals may not drink adequate amounts. Also, chlorinated water may inactivate vaccines. If an animal is incubating the disease before vaccination, the vaccine may not be protective; vaccination against an already contracted disease is usually impossible.
The immune response, being a biologic process, never confers absolute protection nor is equal in all individuals of a vaccinated population. Because the response is influenced by many factors, the range in a random population tends to follow a normal distribution: the response will be average in most animals, excellent in a few, and poor in a few. An effective vaccine may not protect those with a poor response; it is difficult to protect 100% of a random population by vaccination. The size of this unresponsive population varies among vaccines, and its significance depends on the nature of the disease. For highly infectious diseases in which herd immunity is poor and infection is rapidly and efficiently transmitted, such as foot-and-mouth disease, the presence of unprotected animals can permit the spread of disease and disrupt control programs. Problems also can arise if the unprotected animals are individually important, as in the case of companion animals or breeding stock. In contrast, for diseases that are inefficiently spread, such as rabies, 60%–70% protection in a population may be sufficient to effectively block disease transmission within that population, and therefore may be satisfactory from a public health perspective.
The most important cause of vaccination failure in young animals is suppression of an immune response to a vaccine caused by the presence of maternal antibodies. Vaccines may also fail when the immune response is severely suppressed, as in heavily parasitized or malnourished animals. (Such animals should not be vaccinated.) Severe stress, including pregnancy, extremes of cold and heat, and fatigue or malnourishment may reduce a normal immune response, probably due to increased glucocorticoid production.
Modern, licensed vaccines are subjected to rigorous safety and quality control standards and hence are very safe. (This was not always the case in the past, especially when many vaccines were first developed). Nevertheless, they are not always innocuous. The more common risks associated with vaccines include mild toxicity, which may cause injection-site reactions, depression, allergic responses, disease in immunodeficient hosts (modified live vaccines), neurologic complications, and rarely, contamination with other live agents. For example, lesions of mucosal disease may be seen in persistently infected calves vaccinated against bovine viral diarrhea because vaccines contain cytopathic strains. Vaccines that contain killed gram-negative organisms may also contain traces of endotoxins that stimulate release of interleukin-1 and can cause fever and leukopenia and occasionally abortion.
In general, it is prudent to avoid vaccinating pregnant animals unless the risks of not vaccinating are greater. Certain modified live virus bluetongue vaccines have been reported to cause congenital anomalies when given to pregnant ewes. The stress from a vaccination reaction may be sufficient to activate latent infections. For example, activation of equine herpesvirus has been demonstrated after vaccination against African horse sickness. Another adverse reaction is the “sting” that occurs when some vaccines are administered. Some vaccines and vaccine mixtures may cause mild, transient immunosuppression.
In addition to potential toxicity, vaccines, like any antigen, may provoke hypersensitivity. For example, allergic reactions (type I hypersensitivity) may occur in response to the antigens found in vaccines, including those from eggs or tissue-culture cells. All forms of hypersensitivity are more commonly associated with multiple injections of antigen; therefore, they tend to be associated with use of inactivated products. Immune complex (type III) reactions are also potential hazards of vaccination. These may cause an intense local inflammatory reaction or a generalized vascular disturbance such as purpura. An example of a type III reaction is clouding of the cornea in dogs vaccinated against canine adenovirus 1 (CAV1) using CAV1 modified live vaccines. This reaction is not seen with CAV2. Delayed (type IV) hypersensitivity reactions, such as granulomas, may develop at the site of inoculation in response to the use of depot adjuvants. Some chronic inflammatory reactions to long-acting feline vaccines may eventually lead to development of a vaccine-associated sarcoma at the injection site in cats.