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M. Day1
1University of Bristol, Bristol Veterinary School, Langford, United Kingdom
Emeritus Professor Michael J. Day
Chairman, WSAVA Vaccination Guidelines Group profmjday@gmail.comCorrelates of Protection
Protection is the ability of a vaccine to prevent or reduce the effects of infectious disease (depending on the claim for the particular vaccine) when a vaccinated individual encounters virulent infectious agent. In regulatory terms, protection is defined in the context of a challenge experiment. For European vaccine licensing, 80% of vaccinated animals must be protected from disease, while 80% of controls must succumb to the infection. Correlates of protection may be used to indicate whether a vaccinated animal is likely to be protected from challenge with virulent pathogen. It is now well recognized that the presence of virus-specific serum antibody correlates strongly with protection from canine distemper virus (CDV), canine adenovirus (CAV), canine parvovirus (CPV) and feline parvovirus (FPV). In contrast, rabies serology is only used to determine whether vaccinated dogs or cats achieve a mandated antibody titre at a particular time post vaccination for the purposes of pet travel to certain countries.
Numerous studies have shown that dogs that were appropriately vaccinated as puppies (i.e. according
to current guidelines) have persistence of protective serum antibody titres for long periods of time and up
to the lifetime of the animal. The most recent of these studies shows that dogs last vaccinated up to 9 years previously have protective titres of serum antibody [1] and in an experimental setting; such antibody has been demonstrated up to 14 years after the last vaccination [2]. Similar studies clearly show persistence of serum antibody to FPV in vaccinated cats.
Serological Testing
Until recently, the only means of testing for serum antibody specific for vaccine antigens was to submit samples to a specialist diagnostic laboratory. The ‘gold standard’ tests for detection of antibody to CDV, CAV and rabies virus is the virus neutralization (VN) test and for CPV and FPV the haemagglutination inhibition test (HAI). Testing laboratories provide an antibody titre
and will suggest whether that titre is above a threshold that is considered ‘protective’. The titre is defined
as the reciprocal of the last serum dilution giving an unequivocally positive reaction in a serological test. Practitioners must remember that the titre indicates a range and is not a fixed number. For example a titre of 640 indicates that the serum sample contains antibody in a range not less than 320 and not more than 1280
in a doubling dilution series.Recently, in-house test kits have become available for the determination of the presence of protective concentrations of serum antibody against vaccine-preventable viral diseases of the dog and cat. The TitreChekTM test is produced by Synbiotics and marketed by Zoetis, while the VacciCheckTM test is produced by BioGal Laboratories. New test kits continue to emerge (e.g. FastestTM, Diagnostik Megacor, Austria). TitreChek determines whether a dog is protected against infection by CDV and CPV, while VacciCheck tests for protective antibody against CDV, CAV and CPV. A separate VacciCheck kit tests cats for the presence of serum antibody against FPV. In some countries the feline VacciCheck kit still includes feline calicivirus (FCV) and feline herpesvirus (FHV), but these antigens are being removed as the correlation between seropositivity and protection is less clear for these infectious agents. The kits are ELISA-based technologies, but while TitreChek uses a familiar microtitration plate format, the VacciCheck system uses an ‘immunocomb’ in which the reactions occur on spots impregnated into the teeth of a card-like comb and Fastest is a lateral flow procedure. TitreChek and VacciCheck kits have been validated against the gold standards, are simple to use in practice and provide a result within 20–30 minutes. Testing currently costs more than the price of a vaccine. Helpful instructional videos are available on-line (see Maddies Fund: http:// that
work through the performance of each test kit. There are some variations between the two kits: for example both can be run with serum or plasma, but only the VacciCheck kit may be used with a whole blood sample. The ‘read out’ for the TitreChek system is a simple
‘yes or no’ (protected or not) answer, while VacciCheck provides a semiquantitative scoring system.
Both tests claim good sensitivity and specificity and there are now several published papers that independently evaluate the kits against gold standard tests. One
study of the feline VacciCheck test examining antibody
in shelter cats reports a sensitivity of only 49% but specificity of 99% for FPV [3], but another reports 78% and 89%, respectively [4]. In the same animals (in the first study) the sensitivity for FHV was 91% with 97% specificity and for FCV, the figures were 90% and 91%, respectively. The TitreChek kit was evaluated in a study of shelter dogs in Florida, giving a sensitivity of 98%
for CPV (specificity 98%) and a sensitivity of 88% for CDV (specificity 95%) [5]. A further shelter study used
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