I have been involved in a number of discussions lately regarding the concept of testing antibody titers in lieu of vaccinating, and I thought it might be useful to summarize some of the issues involved in this complex topic. I will briefly explain the basic biology of immunization and then talk about the issues surrounding the usefulness of vaccine antibody titers.
How Vaccination Works
The immune system has many mechanisms for identifying and destroying infectious organisms, such as bacteria and viruses, in order to prevent or control disease. The details are bewilderingly complicated, and entire courses, even entire careers in science, are focused on trying to understand how this process works. There are a number of web sites that offer simple overviews of how vaccination stimulates the immune system to protect against infectious organisms (e.g. National Institutes of Health, Centers for Disease Control, National Network for Immunization Information).
Briefly, when a virus or bacterium invades the body, specialized cells that are part of the immune system begin to attack it. Some of these fight off the organism directly, but others communicate with the rest of the immune system to stimulate a host of different responses throughout the body. Part of this global reaction is a memory response. After an initial infection and illness, the immune system learns to recognize the organism so if it sees it again in the future, it can mount a faster and more effective response. Sometimes, this memory provides complete and lifelong immunity. However, sometimes, this immunity is incomplete or only temporary. The difference depends on a lot of factors involving the type of infectious organism and the individual’s immune system.
Vaccines teach the immune system to recognize an infectious organism without producing the actual illness. Usually, vaccines use a killed or weakened version of the infectious organism so the immune system can learn to recognize it without an actual infection and illness. In the future, then, the immune system of a vaccinated individual will be able to generate a faster, stronger protective response to the real organism, therefore avoiding an infection. Again, the effectiveness of vaccination and the duration of this immunity to infection vary and depend on many factors.
There are two basic components to the immune system’s memory of a disease-causing organism. One, called humoral immunity, involves producing proteins called antibodies. These are proteins that recognize a particular organism and help the body to fight it. Antibodies are produced for almost every organism we encounter, naturally or through vaccination, so we all make antibodies to thousands of organisms all the time. We can also get some antibodies from our mothers as babies, through nursing.
The other aspect of the memory response is called cell-mediated immunity. This involves special cells in the immune system which learn to recognize and attack invading microorganisms.
So when we talk about measuring antibody titers, we mean that we are measuring the amount of antibodies in the bloodstream which are produced in response to infection or vaccination for a single microorganism. If we have had an infection or vaccine in the past, we will often have antibodies against that particular organism. These may last for weeks, months, or years. It is important to realize, however, that having antibodies does not always mean we are immune to an infectious organism. If we have too few antibodies, we may be susceptible. And in the case of some organisms, having antibodies is not enough to fully protect us, so we may be susceptible no matter how many we produce. And since we produce antibodies during an infection, having them may not mean we have been vaccinated or had past exposure to an infectious disease, they may simply mean we are currently infected with that disease!
The challenge, then, in using antibody levels to make decisions about vaccination is that the significance of the measurement depends on the details of the biology of the particular organism. When we talk about antibodies and vaccination, we have to talk about one specific disease at a time, because the rules that apply to one disease won’t necessarily apply to another.
Core Vaccines & Antibody Titers
As I mentioned above, for some diseases antibody titers don’t represent immunity or susceptibility very well. Antibodies to common cat disease, for example, such as Feline Herpes Virus (FHV) or Feline Leukemia Virus (FeLV), don’t correlate well with protection against infection. A cat with a high antibody titer against FHV may very well still be susceptible to infection and may benefit from vaccination. And a cat with a high titer for FeLV is probably already permanently infected rather than immune. Antibody titers for rabies and Feline Panleukopenia, however, do correlate with immunity against these diseases.
For dogs, the most important core vaccines are for Canine Distemper Virus (CDV), Canine Parvovirus (CPV), and Rabies. In the case of these diseases, a high antibody titer does usually mean the dog is immune, which would mean additional vaccination for those diseases is not needed at the time the titer is measured. However, the rate at which individuals lose immunity to specific diseases varies quite a bit, so there is no way to predict based on a single titer when that individual will become susceptible again or need additional vaccination.
What most people don’t realize is that while a high titer for some disease, such as CDV, CPV, and Rabies, means a dog is probably immune, a low titer does NOT mean the dog is susceptible and needs to be vaccinated. That is because the other component of the immune system’s memory response, cell-mediated immunity, can protect against infection sometimes even when measured titer levels are low.
So a positive or high titer may mean no vaccine is needed right now, but a low titer does not mean a dog should be vaccinated. In the case of a low titer, we have no way of knowing if that dog is susceptible to these diseases or not.
Specific Titer Tests
You may wonder how we know whether or not a certain level of antibodies measured in the blood mean that individual is protected against that disease. The answer is that the only way to know is through challenge testing. This means that we have to measure antibody levels in a number of individuals with a variety of different titers, then try to infect them with the specific disease we are studying and see which ones get sick and which don’t. This is how cutoff levels for antibody titers have been determined for CDV, CPV, Rabies, and other canine and feline vaccine-preventable disease.
This kind of challenge testing may only be accurate for a specific titer testing method. So if two different laboratories use two different types of titer test, the titer level that is protective will be different, and both would need to do challenge testing to figure out what titer level is protective for the specific test method they each use
Obviously, there are ethical issues associated with this kind of research, and so very little of it is done any more. Most titer tests available have not been validated by challenge testing but have simply been compared to tests which have. This may mean that the values used to determine if an individual is immune to a particular disease are accurate, but it is also possible that they are not. So there is usually some uncertainty about what a “protective” titer really means.
As an example, one popular in-house antibody test sold to veterinarians is called Vaccicheck. This test provides a simple measure of roughly how much antibody an individual dog has against CDV, CPV, and also Canine Infectious Hepatitis. Again, no challenge studies have been done to validate the specific cutoff this test uses, but the test has been compared to what are considered “gold-standard” titer tests. For the canine Vaccicheck test, here are the results of one such study:
B.A. Butler; P.C. Crawford . Accuracy of a Point-of-Care Immunoassay to Determine Protective Antibody Titers For Canine Parvovirus and Canine Distemper Virus. ACVIM Forum, 2013.
Immunoassay sensitivity was 97% for CDV and 99% for CPV. Specificity was 75% for CPV and 79% for CDV. Many of the false positive reactions were in samples with antibody titers near the reference laboratory PAT cutoff. Overall diagnostic accuracy was 90% for CDV and 94% for CPV.
Sensitivity, specificity, and both positive and negative predictive value are somewhat complex statistical topics. Basically, this study showed that when the Vaccicheck test indicated a negative result (low titer level), this was very accurate. Of course, this result doesn’t help us make vaccination decisions because it doesn’t tell us whether or not the individual is vulnerable to infection since cell-mediated immunity may still be providing protection.
The accuracy of a positive result (high titer level) was also pretty good, but not nearly as good as that of a negative level. This means that some dogs will have a positive test, suggesting they are protected, when they really don’t have a high level of antibodies and may or may not actually be immune.
So overall, this test will usually tell us when a dog has a high CDV or CPV titer and does not need to be vaccinated, though it will get some of these wrong. It will more reliably tell us when a dog has a low titer level, but that doesn’t help much us decide if that dog needs to be vaccinated or not. Generally, other in-house titer tests have similar pros and cons. You can see that it can be difficult to make vaccination decisions based on this kind of test.
The legal requirements for vaccination vary by county and even municipality, so it is difficult to make accurate generalizations. Most jurisdictions only require proof of vaccination against rabies, since that is the disease of greatest concern with respect to human health. Most jurisdictions also do not allow titer testing in lieu of vaccination for rabies, though some may. And when titers are used, the only test that is usually accepted is the FAVM from the Kansas State University veterinary laboratory. So while titers are representative of immunity for rabies in dogs and cats, and thus can indicate when vaccination is not needed, they are not often useful practically because they don’t fulfil the legal vaccination requirements.
Titers may or may not be accepted by other parties that require vaccination for other diseases, such as boarding kennels, training facilities, and dog show organizers. Which tests, if any, are accepted is up to the individual organization. So titers may not always be useful in avoiding vaccination if we are vaccinating specifically to meet a legal or institutional requirement.
I have written many times about the subject of vaccine safety. While I believe in avoiding unnecessary vaccination, and while my own recommendations to clients often lead to less frequent vaccination than commonly practiced or suggested in some guidelines, I believe that the fear of vaccines that leads many people to desire to reduce vaccination is unjustified. Vaccines are very, very safe, and many of the specific concerns, such as mercury in vaccines, and autoimmune disease from vaccination, are unproven, exaggerated, or just plain untrue. So while I believe the evidence indicates we can safely vaccinate most dogs and cats far less often than has traditionally been recommended, I do not believe we should use titers or other methods to reduce vaccination out of fear.
Children in the United States and Europe are experiencing a growing risk of preventable infectious disease, and the real harm that comes from such infections, specifically because of a decrease in compliance with sound, evidence-based vaccination recommendations. Mumps, measles, and whooping cough, for example, are injuring and killing children who could have been protected, due mostly to fears among parents which are based on misconceptions or lies. I believe we must be very careful not to follow this same path in veterinary medicine.
So while I see utility for antibody titer testing in some situations, it is distressing that some companies selling these tests seem to be marketing them using fear and the testimonials of individuals who are known opponents of science-based medicine and promoters of irrational anti-vaccine positions and unscientific alternative therapies. Dr. Shawn Messonier, Dr. Karen Becker, Catherine O’Driscoll, and Dogs Naturally Magazine, are some of the entirely unreliable sources to which the Vaccicheck company refers pet owners in promoting their product. We will do far more harm than good for our pets if we base our vaccination decisions on pseudoscience or irrational fear, which is what these individuals often promote, rather than sound science.
- Here is a very clear, informative article on the use of antibody titers in guiding vaccination practices:
Ford, RB. Antibody titers versus vaccination. Today’s Veterinary Practice. May/June, 2013.
2. Here is the American Animal Hospital Association (AAHA) Canine Vaccination Guidelines, which talks specifically and in detail about particular vaccines and comprehensively reviews the available evidence on efficacy, safety, and duration of immunity. The guidelines specifically address titers and generally recommend some uses of them:
Despite the confusion and controversy surrounding antibody testing, these serologic tests are useful for monitoring immunity to CDV, CPV-2, CAV-1, and RV…. The tests are also medically useful to ensure that a dog responds to a specific core virus vaccine and/or to determine if immunity is present in a previously vaccinated dog. Those tests are also used to demonstrate protective immunity as well as DOI.
3. The American Veterinary Medical Association (AVMA) Report on Cat and Dog Vaccines also addresses the subject of titers, but the conclusion is somewhat different from the AAHA guidelines:
…it is currently impossible to determine the immune status of an animal relative to all the infectious diseases of concern without conducting challenge testing. Further, serologic results do not appear to be a sensitive indicator of immune response for some diseases or vaccines in cats and dogs. It was concluded that there are variations within and among laboratories, as well as a lack of validated sensitivity, specificity, and confidence intervals, leading to the conclusion that serologic testing is generally unreliable….
…higher serologic titers are generally associated with greater resistance, but…it is possible for an animal with no titer for a specific organism to have solid resistance to challenge. Conversely, an animal with a titer that is generally regarded as protective for a specific organism may also become ill as the result of challenge, possibly because of overwhelming exposure or immune suppression…
…practitioners are cautioned to consider carefully whether the test proposed has been appropriately validated, thereby providing a predictive value for whether the animal needs to be revaccinated, and includes confidence intervals to help the practitioner determine the risks and benefits of relying on the test results. Practitioners should also determine whether a selected laboratory has a quality control program sufficient to make the test results reliable.
4. The American Association of Feline Practitioners (AAFP) has also issued guidelines for vaccination of cats. These guidelines only comment briefly on the use of antibody titers (also called serology):
It is important to be aware that a variety of methods…are utilized to determine titers.…Titer results in individual cats determined at the same point in time, therefore, may vary depending on the methodology used. When electing to submit serum for antibody titers, it needs to be appreciated that a ‘positive’ antibody titer result obtained on one day is not necessarily predictive of a ‘positive’ titer at any point in the future.
In general, cats having a ‘positive’ antibody titer against FPV are immune. In fact, the protective immunity that develops following FPV vaccination is expected to be sustained for several years. By contrast, serum antibody titers for FHV-1 and FCV may not necessarily correlate well with protective immunity and should not be used to predict protection in the future. Antibody titers to FeLV and FIV do not correlate with immunity and should not be used to determine the need for vaccination. Although feline rabies titers can be determined (by a certificated laboratory) in individual animals, a rabies titer is only an indication of serological response to vaccination. Rabies titers are not recognized as an index of immunity.
In addition, the absence of significant levels of antibody (a ‘negative’ titer) is not necessarily an indication of susceptibility… In some diseases (eg, FHV-1), cell-mediated immunity is important and a cat may be immune even though no antibodies are detectable.
Because antibody titers may not reliably correlate with, or predict, the degree of protection or susceptibility for an individual cat, the Advisory Panel recommends employing defined revaccination intervals rather than measuring antibody titers to assure protection.
Vaccine titers can tell us an individual is immune and does not need to be vaccinated for some specific diseases. For other diseases, a positive titer does not reflect immunity. And a negative titer cannot reliably tell us if an individual is susceptible and need additional vaccination. Therefore, the usefulness of titers in determining if an individual needs to be vaccinated is quite limited. This usefulness is further dependent on the specific kind of titer test used and how it has been validated.
Titers can lead to a reduction in unnecessary vaccination in some cases, if an individual has a titer that can be identified as representative of immunity. However, titers can also lead to an increase in unnecessary vaccinations if animals with negative titers are routinely vaccinated even though they may already be immune.
Titers cannot generally be substituted for legal vaccination requirements, particularly for vaccination against rabies
The vaccines we use are extremely safe, so we have to remind ourselves and our clients that when in doubt it is probably far safer to vaccinate than not to vaccinate, unless there is some know history of adverse vaccine reaction, autoimmune disease, etc. The resurgence of vaccine-preventable disease in children following the decline in vaccination rates is well-demonstrated, and we don’t want to go down that road.
Using scientific evidence concerning the duration of protective immunity following vaccination in a population, and the existing guidelines based on this evidence, is probably a more appropriate strategy for determining how often to vaccinate individuals than is the routine use of antibody titers. Current guidelines for specific vaccines are based on a comprehensive review of existing evidence, and they can be updated as new evidence emerges. While titers may have use in some specific situations, they are not a simple, universal substitute for rational, science-based vaccination guidelines, and they do not offer as reliable an “individualization” of vaccination recommendations as some promoters suggest.