A recently published retrospective cohort study of nearly 500,000 cats vaccinated at 329 hospitals analyzed VAAEs that occurred 30 d after vaccine administration classified by practitioners as nonspecific vaccine reaction, allergic reaction, urticaria, shock, or anaphylaxis. Clinical signs and treatments were reviewed, and the association between potential risk factors and a VAAE occurrence was estimated via multivariate logistic regression.

There were 2,560 VAAEs associated with administration of 1,258,712 doses of vaccine to 496,189 cats (51.6 VAAEs/10,000 cats vaccinated). The risk of a VAAE significantly increased as the number of vaccines administered per office visit increased. Risk was greatest for cats approximately 1 yr old; overall risk was greater for neutered versus sexually intact cats. Lethargy with or without fever was the most commonly diagnosed VAAE. No localized reactions recorded in the 30-d period in these particular cats were subsequently found to be neoplastic when followed for 1-2 yr.

Most VAAEs were diagnosed within the first 3 d of vaccination, and significant risk factors included age, sex, neuter status, weight, and number of vaccines concurrently administered. The VAAE rate within 3 d of vaccine administration in cats (0.48%) was approximately 25% greater than the VAAE rate (0.38%) in dogs reported by the study described above.

In multivariate analysis, the factor associated with the greatest increase in VAAE risk was the number of concurrently administered vaccines or the total vaccine volume administered during the office visit. The increase in risk associated with each additional vaccination (27.5%) in cats was equivalent to the risk recently reported for dogs that weighed < 10kg (< 4.5 lb). When multiple vaccines are simultaneously administered to an animal, the ratio of total volume received per pound of body weight per animal increases, indicating an antigenic dose-response relationship.

Nonspecific systemic reactions with clinical signs of anorexia, lethargy, fever, or soreness were the most common VAAEs observed in cats in the present study. These findings are consistent with results of feline vaccine safety studies, although rates for such reactions may exceed 1%. The causes of these nonspecific reactions may include vaccine organism replication of modified-live vaccines, exposure to endotoxins, adjuvant toxicity, or immune system responsiveness. Clinical signs potentially attributable to immediate-type hypersensitivity reactions and mast-cell degranulation (e.g., vomiting, facial edema, and pruritus) were less common VAAEs in this cat population than reported in dogs. Specific causes of vaccine-induced immediate-type hypersensitivity reactions have not been investigated in cats, but heterologous proteins (e.g., bovine serum albumin) have been implicated as a cause in dogs.

The observed dose-response relationship between the VAAE rate and number of concurrently administered vaccines, as well as the inverse relationship observed between VAAE rate and increasing weight in mature cats, has also been reported in dogs, suggesting that manufacturers may need to reformulate vaccines to reduce protein and excipient concentrations in vaccines for cats and dogs. This will become increasingly important as new vaccines are introduced for disease prevention and veterinarians must consider additional biologics in vaccination protocols. Veterinarians should still limit vaccinations to those needed on the basis of individual risk assessments and should limit the number of concurrently administered vaccinations.

Conclusions and Clinical Relevance–Although overall VAAE rates were low, young adult neutered cats that received multiple vaccines per office visit were at the greatest risk of a VAAE within 30 d after vaccination. Veterinarians should incorporate these findings into risk communications and limit the number of vaccinations administered concurrently to cats.

References: Moore et al, J Am Vet Med Assoc 227:1102–1108, 2005; ibid, J Am Vet Med Assoc 231:94-100. 2007.