Utilization and interpretation of serologic titers

In human medicine, the efficacy of modern vaccines is established and monitored primarily on the basis of standardized serology (“titers”) in conjunction with large-scale clinical trials and usually substantial centralized disease-reporting processes from vaccinated populations.111 A similar approach has been applied to some extent in livestock medicine. This has been facilitated by large vaccinated populations and driven by economic imperatives; immunity favorably affects production parameters. Data deriving from such studies are nearly absent in canine populations.

Studies of experimental infections to determine vaccine efficacy in dogs generally involve small numbers of animals and may use challenge organisms and methods that do not reproduce naturally occurring diseases. In addition, vaccine efficacy and licensing studies generally use purebred beagles with limited genetic heterogeneity. There are relatively few studies conducted in household dogs. Understanding these limitations, as well as the biological reality that vaccines almost never protect 100% of the population 100% of the time, is essential to convey reasonable expectations of vaccine efficacy to clients.

“Protective titers” for CDV, CPV, and to a lesser extent CAV-1 have been of most interest to general practitioners. These viruses often cause lethal infections in naïve dogs and comprise the core antigens for which there are very effective vaccines. Generally, laboratories determining titers have used VN tests for CDV and HI tests for CPV.112–114 Both are bioassays and report results as titers, which are dilutions of antibody. Both VN and HI tests measure antibodies to viral surface proteins that directly relate to neutralization of the virus (VN) or are a surrogate for actual neutralization (HI). In contrast, depending on how the test antigen is prepared, ELISA tests can measure antibody responses that are not involved in protection, such as responses to internal nuclear proteins. Results are generally reported as “units,” not titers.

Interpretation of titers can be difficult for several reasons. First, by their nature, they are subject to intralaboratory and interlaboratory variation. This issue was at least implied in seminal studies. 112,113 Second, there is no readily available documentation of standardization or comparative results of these or other tests when performed in different laboratories. This makes it difficult to interpret a titer, especially if it is not very low or very high. Lastly, at best, the determination of “protective titers” has been based on limited data. These data were thoroughly reviewed 20 years ago.112 Nothing more substantive has become available since then. ELISA-based inclinic antibody detection tests have been available for CPV and CDV for more than 20 years.115,116 HI and VN tests, respectively, were used as “gold standards” to determine their sensitivity and specificity, as it relates to a “protective titer.”115–117 Commercial ELISAs have been applied in shelter populations outside of the laboratory and further compared with HI and VN tests.117,118 Such applications have provided no further basis for a determination of “protective titers,” primarily because the titers or amounts of antibody were not correlated with clinical outcomes. Recognizing these limitations, no values for “protective titers” are indicated in these guidelines, although some commercial laboratories will provide them.

After the disappearance of maternal antibodies, the presence of any detectable antibody (a titer) indicates, by definition, that an immune response to vaccination or exposure to an antigen involving at least B and helper (CD4+) T cells has occurred.94 The presence, or absence, of antibody is not necessarily indicative of coincident cell-mediated immune responses, or their absence.94 Altogether, a titer, almost regardless of the amount, is not necessarily indicative of protection or susceptibility. Rather, it is more complicated than that.119 Disease in the individual animal results from the interaction of host, pathogen, and environmental cofactors. It can be misleading to forecast an outcome on the basis of one cofactor: a titer.

Routine administration of commonly used vaccines has been associated with uncommon to rare adverse events in dogs.52,120 Currently, for the core antigens, most practicing veterinarians have adopted a 3 yr protocol. Unlike in human medicine, it is based on very limited population-based data involving disease reportage, and experimental challenge studies directly comparing the responses in annually versus triennially (or any other interval) vaccinated dogs are lacking. Altogether, routine “titer testing” to ascertain the necessity to revaccinate at currently recommended intervals is not usually advised, except in cases in which dogs have a history of adverse responses to vaccination, there is a suspicion of vaccine-related autoimmune disease, or when owners express resistance or hesitancy to having their dogs vaccinated or boostered—in which case client communication and education may help overcome this hesitancy.

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