Michael J. Day, BSc, BVMS(Hons), PhD, DSc, DECVP, FASM, FRCPath, FRCVS
The delivery of vaccination to dogs and cats has undergone fundamental change in the past decade. In response to questions over vaccine safety, guidelines groups have introduced new vaccination schedules that have been accommodated by vaccine manufacturers introducing products with extended duration of immunity (DOI) and products with fewer antigenic components. The newest advance in vaccinology is the availability of simple in-practice test kits that demonstrate whether an individual animal has serological evidence of protection. These test kits can now inform decision making about vaccination in practice.
Correlates of Protection
For canine distemper virus (CDV), canine parvovirus (CPV), canine adenovirus (CAV) and feline parvovirus (FPV), the presence of serum antibody able to neutralize infectious virus and prevent infection and disease provides an extremely strong correlate of protection. Seroprotection is classically measured by the virus neutralization (VN) and haemagglutination inhibition (HAI) tests. There is excellent correlation between a positive VN test and protection for CDV, CPV, CAV, FPV and rabies. There is an excellent correlation between a positive HAI test and protection for CPV and FPV. For feline calicivirus (FCV) the correlation between a positive VN test and protection is considered only good to fair (as secretory IgA provides a better measure) and for feline herpesvirus (FHV) the correlation between positive VN test and protection is only fair (as CMI is a better correlate of immunity).
In-House Test Kits
There are now two companies that produce in-house test kits for determination of protective serum antibody to CORE infectious diseases post-vaccination. Both test kit systems are simple to use, provide a rapid answer (protection or not) within 20–30 minutes, and are relatively inexpensive (costing around the same for testing as for revaccinating the animal). Both test kit systems have been validated independently and correlated with gold standard tests by a number of diagnostic laboratories. The test kits are the TiterCHEKTM system (manufactured by Synbiotics and now owned and distributed by Pfizer) and the VacciCheckTM system (produced by Biogal Laboratories). The TiterCHEKTM system provides a yes-no (protected or not protected) answer for CDV and CPV. The VacciCheckTM system provides a semiquantitative score for serum antibody titres against CDV, CAV and CPV. A feline VacciCheckTM system provides scores for serum antibody titres against FPV, FCV and FHV. The kits have very good overall sensitivity (detection of samples with antibody from those seropositive by gold standard) and specificity (detection of samples without antibody by those seronegative by gold standard). A set of excellent 'You Tube' videos produced by the US Charity 'Maddies Fund' is available on the web that provide very clear instruction on how to perform and interpret each of these test systems.
Applications of In-House Testing
To Determine Puppy Protection and Detect Genetic Non-Responders
The use of in-house test kits provides a simple measure of whether a puppy (CDV, CAV, CPV) or kitten (FPV) is protected after the initial series of early life vaccinations. WSAVA guidelines recommend the final CORE vaccination at 14–16 weeks. The puppy can be tested from 2 weeks after this vaccination (typically at 18 weeks). Seropositivity at this stage indicates that the pup has made an endogenous immune response to vaccine as there can be no MDA remaining at this time. A puppy that is seronegative at 18 weeks should be revaccinated (perhaps with an alternative product) and then tested again 2 weeks later. A positive result indicates protection. A second negative result may indicate that the pup is either a 'low responder' or a 'non-responder.' Performing a gold standard test at this stage may show the low antibody titre typical of a low responder dog. Such an animal will be protected from clinical disease but not from infection. Alternatively, the dog may lack antibody and be a genetic non-responder that is incapable of ever making an immune response to that particular antigen. Such dogs are therefore susceptible to infection and disease for life. Dogs of the Rottweiler breed have a higher proportion of genetic non-responders to CPV and rabies virus vaccines. Although non-responder Rottweilers are now no longer recognized in the US (the gene pool has selected against them), they are still seen in Europe. Note that genetic non-responders are generally unable to respond to one (rather than all) CORE vaccine antigens. The estimated prevalence of non-responders (US data) for CPV is 1 in every 1000 dogs and for CDV 1 in every 5000 dogs. CAV non-responders are very rare (estimated < 1 in every 100,000 dogs).
To Decide About Vaccination of a 'Lapsed' Adult Dog
Much is currently made of revaccinating 'lapsed' adult dogs or adult dogs adopted without a vaccination history. Such dogs may not actually require vaccination because they have been previously vaccinated or in some instances have acquired natural immunity from field exposure to virus. Owners may therefore be offered serology rather than automatic vaccination in this circumstance.
To Minimize Risk in an Animal Previously Having an Adverse Reaction to Vaccine
Adverse reactions of a wide spectrum are recognized post-vaccination in dogs and cats. The prevalence of these is low and most are mild and transient effects. However some (e.g., canine immune-mediated disease) are potentially life-threatening and if there is a suspicion that vaccination might have been a trigger for a disease then such animals should be subject to rigorous benefit-risk analysis before revaccination is considered. For CORE vaccine antigens, this decision is now made simpler by the availability of in-house serology. A dog with serum antibody to CDV, CAV and CPV does not require revaccination with MLV CORE vaccines and serious consideration should be given to which NON-CORE products such an animal receives.
Serology Replacing Revaccination in an Annual Health Check
In the US and increasingly in Europe, the Annual Health Check concept is gaining momentum. So too is the adoption of triennial CORE revaccination schedules for adult animals. However, many US practices have now moved on again in this rapidly changing arena. Instead of offering triennial CORE revaccination, these practices are now offering the alternative of triennial serological testing using one of the in-house systems. Dogs that are seropositive (or cats seropositive for FPV) are not revaccinated with CORE vaccines as these are not required. NON-CORE vaccines may still be used annually and for cats at risk, FCV and FHV revaccination might be considered annually. Where this approach is used, the testing interval is reduced to annually for senior animals (dogs > 10 years and cats > 15 years) to ensure that immunosenescence (aging of the immune system) is not an issue.
Management of Disease Outbreaks in Shelters
One of the most valuable applications of in-house serology has been in the management of infectious disease outbreaks in shelters - specifically for CDV, CPV and FPV outbreaks. The ability to rapidly and cheaply test populations in order to identify animals that are protected or susceptible, has allowed many animals to live that might otherwise have been euthanised as they were of unknown status.
In the face of a disease outbreak, all animals currently resident within the shelter should be tested. Those that are seropositive are protected and will not become infected or die. This protected population should be separated from low or negative responder animals that should be isolated. The susceptible population should not be adopted out of the shelter until after at least 2 weeks for CPV or FPV or until after at least 6 weeks for CDV (reflecting the incubation periods of the diseases). The susceptible population might be retested after these intervals.
The second population to be considered are those animals that are wishing to enter the shelter. These should also be tested before considering admission. Seropositive animals may enter as they are protected from disease. Seronegative animals should be vaccinated and then ideally sent to foster homes and not allowed to enter the shelter until they have seroconverted (when retested 2 weeks later).
This approach has proven to be very successful in controlling infectious disease outbreaks in shelters. The approach is not applicable to outbreaks of feline infectious respiratory disease complex as serology is not correlated with protection.