Postvaccination adverse events and reactions

Undesired or unexpected consequences after vaccination include failure to provide protection from disease and adverse reactions associated with vaccine administration. Failure to provide protective immunity is primarily of concern in very young or very old dogs. Young dogs most commonly fail to mount a sufficient immune response following vaccination because of the presence of MDA from colostrum. Puppies in some breeds, e.g., Doberman pinschers and rottweilers, have been purported to be immune nonresponders to a standard initial vaccination series, but definitive evidence of this characteristic is lacking.

Questions are sometimes raised about whether multiple vaccines, simultaneously administered, diminish or overwhelm the immune response. Although antibody responses can vary after administration of different vaccines and antigens, there is no evidence of a lack of protective immunity following concurrent administration of multiple antigens or vaccines.

Vaccine efficacy in older dogs is typically related to concerns of immunosenescence, an age-related decline in the function of the immune system. Although geriatric dogs may have a relative diminution of naïve T cells to confront new antigens, these patients generally do not lack memory cells created from previous exposure to antigens in early or mid-life.121

Adverse postvaccination reactions may be (1) caused by inappropriate administration of a modified-live product, (2) secondary to innate immune responses to the vaccine, (3) specific cell-mediated or humoral immune responses to vaccine components, or (4) induced by vaccine antigens that return to virulence (unlikely in appropriately tested and licensed vaccines).

Localized cell-mediated immune reactions or generalized systemic responses can occur after vaccination. Type I hypersensitivity reactions have been linked to vaccination, but vaccine associations with other immune-mediated diseases, e.g., immune-mediated thrombocytopenia, immune-mediated hemolytic anemia, and immunemediated polyarthritis, are less consistent.122–126 This may indicate that factors besides vaccine antigens are responsible for immune disease sequelae following vaccination.

Adverse reactions, as well as desirable immune responses, are genetically influenced in some cases. Immunogenetics is a developing investigative field for adverse drug and vaccine reactions in people127,128 but is basically unexplored in veterinary medicine. Although some breeds have been identified as at increased risk of vaccine reactions,52 breed (a phenotype) is a crude indicator of genetics. More likely, genetic predisposition for individuals exists within some family lines, thus selectively increasing risk overall for some breeds. Owners should be informed that adverse event risk occurs at the individual patient level.129

In genetically predisposed individuals, undesirable immune responses can be triggered by various vaccine antigens.123,130 In dogs, IgE reactivity has been detected against components of cell culture media used to propagate vaccinal viruses and other pathogens.Mostly, the offending substances are xenogeneic (to dogs) proteins, such as in fetal calf serum, e.g., bovine serum albumin, gelatin and casein.131 In other words, the antigens of concern are typically vaccine components that are not the label (pathogen) antigens. Thus, identification and quantity of these antigens are not part of manufacturer labels.

Although genetic predisposition cannot be altered, adverse event risk can be diminished by reducing the quantity of vaccine antigens presented to the patient’s immune system. Because antigens of concern are not the label antigens, combination vaccines containing multiple pathogens do not inherently carry more adverse event risk than single-component vaccines. Because of the way rabies vaccine virus is propagated, single-component rabies vaccines may have more adverse event risk, as they have a more diverse array of proteins than combination vaccines containing other viruses that are propagated similarly, or other single-component vaccines.132

Reducing antigenic stimuli can be achieved by reducing the number of vaccines administered at a single office visit. This is a particularly useful approach in small dogs.52 Reducing the administered volume (“split dosing”) for any vaccine below the manufacturer’s recommended volume is not advised, because the USDA and manufacturer have not approved such reductions. Therefore, this practice could involve the assumption of liability.12

Reducing the number of vaccines administered at a single office visit may necessitate additional office visits in order to provide necessary vaccine coverage and complete protection. Although comparison studies have not been performed, at least 2 wk is recommended between vaccines to allow the heightened immune response from the most previous vaccination to subside.

If possible within guidelines and manufacturer recommendations, administering vaccines nonparenterally, e.g., mucosally or IN, can also reduce adverse event risk.

A common question is whether at-risk patients should be pretreated with diphenhydramine before vaccination. If the risk is hypothetical, i.e., involving an at-risk breed but in cases in which no previous reactions have occurred, pretreatment as a precaution is generally not recommended. Although prevaccination administration of diphenhydramine may prevent type I hypersensitivity reactions, the lack of any subsequent reaction does not actually prove the pretreatment was beneficial or necessary.

If the vaccination risk involves a dog with a history of previous vaccine reaction, one cannot presume reactions will automatically recur. Precautions such as limiting the number of vaccines administered are prudent, as is prevaccination administration of diphenhydramine. Single anti-inflammatory doses of glucocorticoids, if administered, do not impair humoral responses to vaccination.133,134 If the vaccination risk involves a patient with an existing immunemediated disease, consideration should be given to the stability and condition of the patient, the need for vaccination, and prudent ways to minimize adverse event risk.

If vaccines are administered to patients with existing medical conditions or health concerns, clients should sign an informed consent statement as increased risk of disease may result if the dog’s immunocompetence is compromised. When a dog experiences a possible adverse event, the veterinary team should report the specific patient and vaccine information to the vaccine manufacturer and/or the USDA. ( biologics/adverse-event-reporting/ct_vb_adverse_event).

These guidelines are generously supported by Boehringer Ingelheim Animal Health, Elanco Animal Health, Merck Animal Health and Zoetis Petcare.