Titres….ugh. I spend a lot of time answering questions about these, with little data to go by.
To start, what are titres?
Titres are a measure of antibody levels. Antibodies are produced by the body in response to infection or vaccination.
What do titres tell us?
They tell if a specific antibody is present and the amount of it (or a relative idea of the amount that is present). No more, no less. It doesn’t mean that the antibodies are actually useful or that the amount that’s present is enough to prevent infection. It just says whether or not the specific antibody we’re assessing is present.
What don’t titres tell us?
They don’t tell us anything about other parts of the immune system, most importantly ‘cell mediated immunity’. I won’t get too far into immunology here but 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 does not involve antibodies and is driven by the action of T cells. Measuring antibodies tells us nothing about the cell-mediated immune system.
What is a ‘protective titre’?
Good question. By definition, it would be a titre that is known to be high enough to protect against infection after exposure. That could be from good prospective studies that follow animals with known titres or through experimental studies. However, we don’t have much data about that (almost nothing that applies to field situations).
But labs report, cut-offs for titres so that’s a 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 where those values came from and it’s exceedingly unlikely they are based on any study of protection from actual disease.
Here’s another statement from the 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 means 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 that. It’s a potentially appealing approach in some situations (although most 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 that might be enough antibody to work or because of cell mediated immunity. If there’s consideration for stopping vaccination (e.g. adverse reactions, vaccine hesitancy), I focus more on the vaccine history (number of previous doses and timing) and risk of exposure than I do on titres. 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. In some, there’s an option for a vaccine exemption for dogs that have a medical reason that vaccination should be avoided. However, that just exempts the dog from the legal requirement. It doesn’t exempt it from the implications of 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 month strict quarantine or euthanasia. It doesn’t matter why the dog wasn’t vaccinated or if there is a known rabies titre. A good rabies titre would be some reassurance that the dog is likely protected but it’s not enough of a guarantee to influence control measures.
But there are specific titre tests for rabies that are required by some countries for imported dogs. Those should be good, right?
Good, in terms of accurate, with well-described, standard methods? Yes.
Good to prove that an animal has been vaccinated against rabies? Yes.
Good to show the animal is protected against rabies? Not necessarily. We have a standard cut-off but it’s not one that we can guarantee means the animal is protected (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 provide a good 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?
For me, titre testing is best to say whether the animal was vaccinated or has previously been infected. It’s probably of most use in a shelter situation where animals most often come in with no vaccine history. If they have a titre, they have either been vaccinated or been previously infected (and are quite possibly immune). That can be useful information for managing the animal (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 an 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 this series of questions provides me more insight into immune status and the need for vaccination.
- How old is your dog/cat?
- What has it been vaccinated with and when?
- Tell me a bit about your dog’s lifestyle.
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.
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.