Titres… ugh. I spend a lot of time answering questions about titres, with little data to go on.

What are titres?

Titres are a measure of antibody levels in the bloodstream. Antibodies are produced by the body in response to infection or vaccination.

What do titres tell us?

Titres indicate whether a specific antibody is present in the blood, and how much (or a relative idea of the amount of antibody that is present). No more, no less. It doesn’t mean that the antibodies are actually useful, or that the amount present is enough to prevent infection. It just tells us whether or not the specific antibodies we’re assessing are there.

What do titres not tell us?

Titres don’t tell us anything about other parts of the immune system, most importantly the components that make up what’s called “cell-mediated immunity.” I won’t get too far into the immunology here, but basically there are two main arms of the immune system, humoral immunity and cell-mediated immunity. Humoral immunity is driven by B cells (a type of white blood cell) that produce antibodies to specific antigens. Cell-mediated immunity is driven by the action of T cells (a different type of white blood cell) and does not involve antibodies. Both are very important for fighting infections, but measuring antibodies tells us nothing about cell-mediated immunity.

What is a “protective titre?”

By definition, a titre that is known to be high enough to protect against infection after exposure to a specific pathogen would be considered “protective.”  This can be determined through prospective studies following animals with known titres that are naturally exposed to the pathogen, or through experimental studies in which animals are exposed in a laboratory setting, and then watching/testing to see which animals still get sick or stay healthy. However, we don’t have much data about protective titres for disease in animals (and almost nothing that applies to field situations).

But labs report “cut-offs” for titres, so that’s the protective titre, right?

Here’s a statement from the 2022 AAHA Canine Vaccination Guidelines:

• “…, at best, the determination of “protective titers” has been based on limited data. These data were thoroughly reviewed 20 years ago. Nothing more substantive has become available since then. ELISA-based in-clinic antibody detection tests have been available for CPV and CDV for more than 20 years. HI and VN tests, respectively, were used as “gold standards” to determine their sensitivity and specificity, as it relates to a “protective titer.” Commercial ELISAs have been applied in shelter populations outside of the laboratory and further compared with HI and VN tests. 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.”

Some labs will report cut-offs, but it’s not clear from where those values came, and it’s exceedingly unlikely they are based on any study of protection from actual disease.

Here’s another statement from the 2022 AAHA Canine Vaccination Guidelines:

• “Altogether, a titer, almost regardless of the amount, is not necessarily indicative of protection or susceptibility. Rather, it is more complicated than that. 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.

All that said, the presence of a detectable titre is probably a good sign and, in general, higher is better. However, what specific titres mean in terms of protection is impossible to say. No one should ever interpret a titre as indicating there’s no risk or no need to vaccinate. Similarly, a very low titre shouldn’t be interpreted as zero protection. We simply don’t know what those values mean.

Can titre testing be use lieu of vaccination?

This is the most common question about titres, and I’m not overly comfortable with it. It’s an appealing approach in some situations (although more costly that vaccinating). A high titre probably means good protection. A low titre might mean protection is poor, but it’s quite possible that the animal is still protected because there’s still sufficient antibodies and/or cell-mediated immunity (which we can’t measure directly). If there’s reason to consider stopping routine vaccination (e.g. adverse reactions, vaccine hesitancy), I focus less on titres and more on the animal’s vaccination history (i.e. number of previous doses and timing) and the animal’s ongoing risk of exposure. Rarely would a titre change what I’d recommend.

I’m required by law to have my pet vaccinated against rabies. Does a positive titre mean I can get an exemption?

No (or at least not anywhere that I know about). Rabies vaccination is required in many jurisdictions, including in Ontario for all dogs, cats and ferrets over 3 months of age. Sometimes exemptions can be made for pets that have a medical reason that vaccination should be avoided. However, that only exempts the pet from the legal requirement to be vaccinated, it doesn’t exempt it from the implications of a potential rabies exposure. If a dog or cat is exposed to a rabid animal, its vaccination status is a key determinant in what happens, ranging from a short observation period to 6 months strict quarantine (or even euthanasia). It doesn’t matter why the dog wasn’t vaccinated or if it has a high rabies antibody titre. A good titre would be some reassurance that the dog is likely protected, but it’s not enough of a guarantee to change the post-exposure management requirements.

There are specific titre tests for rabies that are required by some countries for importation of dogs. Those should be good, right?

“Good” in terms of accurate, with well-described, standard methods? Yes.

“Good” enough to prove that an animal has been vaccinated against rabies? Yes.

“Good” enough to show the animal is protected against rabies? Not necessarily.

While there is a standard cut-off for rabies titres for the purposes of international travel, it does not guarantee the animal is protected from  infection.  For good reasons, no one has done live animal studies looking at what titres protect dogs and cats from rabies virus infection. The 2022 AAHA Canine Vaccination Guidelines state “Antibody titer levels as correlates of protection have not been established for rabies, and serologic testing is not considered a substitute for vaccination.” So, rabies titres are best to prove that an animal has been vaccinated and provides a reasonable suspicion that they would be protected, but are far from a guarantee. That’s why we want to vaccinate whenever possible.

What is titre testing good for?

To me, titre testing is useful to say whether an animal has been vaccinated or has previously been infected. It’s probably of most use in a shelter situation where animals often come in with no vaccination history. If they have a titre, they have either been vaccinated or been previously infected (and are quite possibly immune to reinfection, at least for a while). That can be useful information for managing the animal (e.g. where to house it, whether to foster it, priority for vaccination, isolation approaches), particularly in situations where there’s an outbreak or high disease exposure risk.

There might also be value in testing dogs and cats whose last “core” vaccine was at 16 weeks of age. That’s the age where we assume they’ll respond to the vaccine, but some don’t. Personally, if in doubt, I’d rather just give another dose at 20 weeks (as per guidelines) but if there’s a reason to avoid vaccination, titres could be considered to see if there’s been a response to any of the earlier vaccines. I’d be looking at a yes/no versus a number, as with shelter admissions.

Beyond that, I’m less convinced and think the following series of questions provides more insight into immune status and the need for vaccination:

• How old is your dog/cat?
• With what has it been vaccinated and when?
• What is your pet’s lifestyle, including exposure to other animals?

With those, I can have a pretty good idea about immune protection and disease risk, maybe as much (or more) than if I had a titre measurement.

I think this concludes our vaccination question series, but if there are other questions, send them my way, and we can move on to Part 6.