Michael R. Lappin, DVM, PhD, DACVIM
Professor, Department of Clinical Sciences, Colorado State University, Fort Collins, CO, USA
Feline Vaccine Serology
Feline vaccines occasionally induce side-effects including an association with formation of soft tissue sarcomas. Adjuvanted rabies virus and feline leukemia virus vaccines cause the most inflammation and have been linked most frequently to tumor production but soft tissue sarcomas have also developed at the site of subcutaneous inoculation with modified live or killed feline herpesvirus 1 (FHV-1), calicivirus (FCV), and panleukopenia virus (FPV) vaccines (FVRCP). Recently, administration of FVRCP vaccines parentally has been linked to the production of antibodies against the cell line used to grow some vaccine viruses. In some cats, those antibodies cross react with renal and other tissues. While a disease association has not been shown, it is another factor to consider when determining an optimal vaccination protocol for an individual cat.
The duration of immunity for some feline vaccine antigens is known to be > 3 years. Thus, the American Association of Feline Practitioners/Academy of Feline Medicine (AAFP/AFM) and others have questioned the need for annual vaccination with FVRCP products after the 1 year booster immunization. It is unknown to what extent humoral or cell-mediated immunity is responsible for the protection elicited by FPV, FHV, or FCV vaccination. The humoral immune response to FCV, FHV-1, and FPV vaccines can be readily measured by the detection of virus-specific antibodies. Quantification of cell-mediated immune responses is difficult and is not typically performed on a routine diagnostic basis. In general, presence of serum antibodies indirectly suggests that cell-mediated immune responses are also intact as B lymphocytes (humoral) require T lymphocyte (cell-mediated) help to maintain antibody production. Regardless whether humoral immunity is responsible for protection, if the presence of virus-specific antibody correlated with protection from challenge with FPV, FCV, and FHV-1, serologic screening of individual vaccinated cats could be used to predict vaccine needs. In one study, serum antibodies against FHV-1, FCV, and FPV could be detected in 100% of cats inoculated twice with a killed FVRCP product 3 years previously. When these cats were challenged with virulent virus 7.5 years after vaccination, the cats were 100% protected against FPV (Scott et al, 1999). When challenged with virulent FHV-1 and FCV, clinical signs of disease in the vaccinated cats were decreased 52% and 63%, respectively, when compared to unvaccinated controls.
Virus neutralization (FHV-1, FCV) and hemagglutination inhibition (FPV) assays have classically been used to assess antibody responses to FVRCP vaccines. These assays are labor intensive, are only available in specialized laboratories, and are usually not standardized between laboratories. There are now other techniques on the world market for detection of antibodies. For example, enzyme-linked immunosorbent assays (ELISAs) using whole virus or virus infected cell preparations have been used for detection of antibodies specific for FCV and FHV-1 and are potentially more sensitive than virus neutralization techniques. In addition, ELISAs are technically less complicated, can be standardized for use in multiple laboratories, and can be adapted for use in the veterinary clinic.
In one study, serum antibody responses to feline panleukopenia virus (FPV), feline herpesvirus 1 (FHV-1), and feline calicivirus (FCV) were compared to resistance to challenge with the respective virulent viruses in experimental cats. In total, 72 laboratory-reared cats were used and then adopted to private homes. In 4 separate experiments, cats were either vaccinated against FPV, FHV-1, and FCV using an intranasal vaccine or one of two subcutaneous vaccines or maintained as unvaccinated controls. Between 9 and 36 months after vaccination, the cats were challenged with virulent viruses using USDA protocols for vaccine approval. ELISAs for detection of FPV, FHV-1, and FCV antibodies were developed (HESKA Diagnostic Laboratory, Fort Collins, CO). Serum antibody levels as determined by ELISAs as well as hemagglutination inhibition (HI) for FPV and serum neutralization (SN) for FHV-1 and FCV (New York State Veterinary Diagnostic Laboratory) were correlated to resistance to viral challenge.
When used with vaccinated cats, the positive predictive value of FPV, FHV-1, and FCV antibodies as detected by ELISAs were 100%, 90.5%, and 100%, respectively. When used with vaccinated cats, the positive predictive value of FPV, FHV-1, and FCV antibodies as detected by HI or SN were 100%, 91.3%, and 100%, respectively. The ELISAs were also applied to sera from 276 client-owned cats. The seroprevalences for FPV, FHV-1, and FCV were 68.5%, 70.7%, and 92.4%, respectively. It was concluded that when used with vaccinated cats, positive antibody tests for FPV, FHV-1, FCV correlate to resistance to challenge in most cats regardless of vaccine type or interval. Whether use of serum antibodies to predict resistance to infection with FPV, FCV, and FHV-1 would be affected by route of vaccine administration or vaccination interval was previously unknown since only a single long term study using one product was reported. In the study described, two FPV and FHV-1 vaccines and 3 FCV vaccines were assessed. Additionally, interval between vaccination and challenge varied from 9 months to 31 months for FHV-1 and FPV and from 9 months to 36 months for FCV. Positive predictive values of the serum antibody tests were similar regardless of the vaccine or vaccine interval.
Since the majority of client-owned cats are seropositive for these agents with antibody titers that predict resistance to infection, use of arbitrary vaccination intervals is likely to lead to unnecessary vaccination of some cats. If validated assays are available, serological testing for prediction of FVRCP antigen needs appears to be appropriate for use in lieu of arbitrary vaccination intervals.
It is possible that in the future, serological tests could be used to predict vaccine needs for other antigens, potentially feline leukemia virus and rabies virus. However, at this time, information concerning use of serological tests for other feline vaccine antigens is largely unavailable and is not recommended.
Canine Vaccine Serology
Like cats, vaccine associated side-effects in dogs are rare. However, over-vaccination occasionally causes problems and so if a vaccine antigen is not needed, it should not be given. For dogs in the United States, core vaccines include canine distemper virus, parainfluenza, adenovirus 2, parvovirus, and rabies. Puppies are generally vaccinated every 3-4 weeks with distemper, parvovirus, and adenovirus 2 vaccines until 14-16 weeks of age. At one year of age or one year later the dog should return for a booster vaccination. After one year of age, risk of infection by canine distemper virus, parainfluenza, adenovirus 2, and parvovirus should be assessed yearly while performing a physical examination and checking for enteric parasites.
In several studies, canine distemper virus titers and canine parvovirus titers suggestive of resistance were detected in >95% of the dogs tested, respectively. Canine parvovirus vaccines may provide life-long immunity and distemper virus titers are detected for up to 10 years in many dogs. Thus, in low risk dogs, modified live DA2PP vaccines should be administered no more often than every third year. In addition to serological studies, challenge studies from several vaccine manufacturers have shown at least 36-57 week duration of immunity to infectious canine adenovirus, distemper, and parvovirus on challenge.
Positive serologic tests for canine distemper virus, canine adenovirus 1, and canine parvovirus are predictive of resistance. If validated assays are available, serological testing for prediction of these vaccine antigen needs appears to be appropriate for use in lieu of arbitrary vaccination intervals.
For some vaccine antigens, serology is not predictive. For example, some dogs with serological responses to Borrelia burgdorferi and leptospires can still be infected with the organism. For other vaccine antigens, information or validated assays are not currently available.
1. Lappin MR, et al. Prediction of resistance to feline parvovirus, feline herpesvirus 1 and feline calicivirus challenge utilizing serology. J Am Vet Med Assoc 2002; 220: 38-42.
2. Lappin MR, et al. Investigation of the induction of antibodies against Crandell-Rees feline kidney cell lysates and feline renal cell lysates after parenteral administration of vaccines against feline viral rhinotracheitis, calicivirus, and panleukopenia in cats. Am J Vet Res 2005; 66: 506-511.
3. Mouzin DE, et al. Duration of serologic response to three viral antigens in cats. J Am Vet Med Assoc 2004; 224: 61-66.
4. Mouzin DE, et al. Duration of serologic response to five viral antigens in dogs. J Am Vet Med Assoc 2004; 224: 55-60.
5. Paul MA, et al. 2006 AAHA Canine Vaccine Guidelines. J Am Anim Hosp Assoc 2006; 42: 80-89.
6. Richards J, et al. Feline vaccine selection and administration. Compend Cont Ed Pract Vet 2001; 23: 71-80.
7. Schultz RD. Duration of immunity for canine and feline vaccines: A review. Vet Microbiol 2006 April 18, Epub ahead of print.
8. Scott FW, Geissinger C. Duration of immunity in cats vaccinated with an inactivated feline panleukopenia, herpesvirus, and calicivirus vaccine. Fel Pract 1997; 25: 12-19.
9. Scott FW, Geissinger CM. Long term immunity in cats vaccinated with an inactivated trivalent vaccine. Am J Vet Res 1999; 60: 652-658.
10. Scott-Moncrieff JC, et al. Evaluation of antithyroglobulin antibodies after routine vaccination in pet and research dogs. J Am Vet Med Assoc 2002; 221: 515-521.
11. Tizard I, Ni Y. Use of serologic testing to assess immune status of companion animals. J Am Vet Med Assoc 1998; 213: 54-60.
12. Twark L, Dodds WJ. Clinical use of serum parvovirus and distemper virus antibody titers for determining revaccination strategies in healthy dogs. J Am Vet Med Assoc 2000; 217: 1021-1024.