Antibody Titer Testing as a Guide for Vaccination in Dogs and Cats

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.

Legal Issues
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.

Vaccine Safety
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.

Additional Information

  1. 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.

Bottom Line
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.

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29 Responses to Antibody Titer Testing as a Guide for Vaccination in Dogs and Cats

  1. Pingback: Titera and evidence - YorkieTalk.com Forums - Yorkshire Terrier Community

  2. skeptvet says:

    I have been involved in a thread on Facebook discussing this topic, and some good questions have been raised which I answered there. I thought I would copy those responses here since I suspect some of the same questions may occur to readers of this post.

    On Facebook, I was asked why I disagreed with Dr. Becker, Dr. Ron Schultz, and others who claim that, at least for CDV and CPV, a positive titer after initial vaccination at 4 months of age indicates lifelong protection and so further vaccines shouldn’t be given, at least unless titer tests showed low titers:

    It’s not about who I like or don’t like, it’s about the science. The AAHA and AVMA guidelines involve numerous respected experts, including Dr. Schultz, who was actually one of the authors of the AAHA guidelines. People often choose which expert to believe or to quote based on whether what that person says agrees with what their own point of view. But it is more reliable to look at the evidence itself, rather than choose one individual to follow.

    As far as titer testing, the question whether or not to use it ultimately comes down to whether our pets/patients will be safer and healthier if we do than they are if we don’t. That means balancing the risks and benefits of vaccination and of testing or not testing.

    In terms of duration of immunity, the AAHA guidelines on CDV and CPV review the evidence and say, “The >/=3 yr recommendation for core vaccines is made on the basis of minimum [duration of immunity] studies over the past 30 yr for canine vaccines. These studies were done by all of the major vaccine companies, as well as by independent researchers. The results of the studies conducted by the major manufacturers for canine core vaccine demonstrated that a minimum DOI for their core vaccines (CDV, CPV-2, CAV) was >/=3 yr, based on challenge and/or serologic studies.”

    Some individuals will have longer duration of immunity than others. It is likely that most will be protected at least 5-7 years if they have a positive response to the initial CDV or CPV series. Some may well have lifetime immunity, but the data don’t say that we can assume lifetime immunity in every dog that has a response after 16 weeks of age.

    So given this evidence, I generally recommend an initial series for CDV and CPV, then boosters at 5-year intervals until about 10 years of age. That means, for most dogs 2-3 booster vaccinations. Most vets now boost every three years, so that might mean 4-5 boosters, depending on how long the dogs live and if they stop vaccinating at some point.

    If we titer test annually (because we can’t predict from one test when the antibody levels will decline), then we might choose to skip some or all of these boosters for animals with high titers. This would be fairly safe, though the test does actually have a fairly high false positive rate, so depending on how many dogs in our test population have low titers, a fair number of them could mistakenly test as if they had high titers.

    On the other hand, what do we do with those with negative titers? Since we can’t know if they are protected or not, we would probably be obliged to vaccinate them. But many of them probably aren’t susceptible to the diseases and don’t need vaccination. So we could end up vaccinate some dogs we otherwise wouldn’t have even if they don’t need it.

    Finally, if some dogs have lifelong high titers, we might skip anywhere from two to five vaccinations in a lifetime using the test. Do you really believe this will make these dogs healthier? Vaccines are incredibly safe, and the rate of demonstrable harm is very, very low. So for the cost of testing and the increased chance of over-vaccinating dogs with negative titers we are exchanging the “benefit” of two to five fewer vaccines in a lifetime, which I believe will do virtually nothing to improve health or reduce disease since these vaccines are probably not harming these dogs.

    Again, I’m not saying I am opposed to titer testing. I do it for those clients who request it, and sometimes it leads us to skip a vaccine I might otherwise have given. But it also sometimes gives us no information at all (when the titer is negative), and most vets would feel obliged to vaccinate these dogs regardless of when they had previous boosters. And the bottom line is it is being sold primarily with the idea of making dogs safer by reducing vaccination rates, and I don’t see any evidence that this would actually be the case.

    I want people to have all the facts, and not to make decisions about testing or vaccinating based on being afraid of vaccines, since that has led to great harm in humans. My objection to the Vaccicheck marketing, and the comments of folks like Becker, O’Driscoll, etc, is not personal. It is an objection to their frequent attempts to make people afraid of vaccines when the evidence suggests they shouldn’t be.

  3. Louise H says:

    Thanks for, as always, a clear explanation and summary. I recently raised the possibility of moving away from routine annual vaccinations for my cats and dog with my vets and was told that they offer titration as an alternative, so it was on my list for looking into. Just moving to three yearly for the core vaccines didn’t seem to be an option they recommended, but it looks as if it is the most sensible. I can’t see the point in titrating while the scientific evidence is pretty definite that my animals will still be immune, and once I get to the end of the recommended immunity period I’m happy to just revaccinate.

    I have a question that I know is rather away from the small animal line but I have three young pet backyard pygmy goats which I have vaccinated (off license) using Lambivac. The vaccine instructions recommend revaccination (for sheep) every six months but I haven’t been able to find any information about research into actual protection provided by the vaccine. Do you know of anywhere where I could look? I will dutifully revaccinate them every six months in the absence of evidence to the contrary but I do wonder if it’s really necessary!

  4. skeptvet says:

    I don’t know a darned thing about caprine vaccination, but here are a couple of resources you might find useful:

    Cornell Vet Med School Guidelines

    National Pygmy Goat Association

  5. lorac says:

    thank you for the well-written article and links. my scientific background is in immunology. i’m glad to see that there are more data regarding time of immunity after vaccination in dogs. are there any data on vaccination efficacy and age of dog? especially in elderly dogs. as you know, there’s a decline of efficacy / robustness in elderly humans, and i would expect it to be similar for dogs.

  6. skeptvet says:

    Thanks for the great question. As usual, the amount of evidence available to answer it is far less in the veterinary field than is usual for human medicine. I am only aware of a couple of studies. These seem to suggest that while there are differences in immune response in older animals, these do not appear to influence the efficacy of immunization. But not too much can be made of the scant data.

    Day MJ.Ageing, immunosenescence and inflammageing in the dog and cat.J Comp Pathol. 2010 Jan;142 Suppl 1:S60-9. doi: 10.1016/j.jcpa.2009.10.011. Epub 2009 Dec 14.

    Improvements in veterinary healthcare over recent decades mean that we now have a significant population of geriatric small companion animals. The design of optimum nutritional and vaccination programmes for these aged animals must be underpinned by knowledge of the physiological changes that occur in later life. It is clear that older dogs and cats are affected by the process of immunosenescence and that similar changes occur in these species to those documented in elderly people. The most consistent findings of recent investigations indicate impairment of cell-mediated immune function with age. Senior dogs and cats are generally shown to have reduced blood CD4(+) T cells (with imbalance in Th1 versus Th2 functional activity), elevation in the CD8(+) subset and reduction in the CD4:CD8 ratio. The ability of blood lymphocytes to respond to stimulation by mitogens decreases, as does the cutaneous delayed type hypersensitivity response. By contrast, there is relative preservation of the ability to mount humoral immune responses. Serum and salivary immunoglobulin (Ig)A production increases and IgG concentration remains unaltered with age. Elderly animals generally have persisting vaccinal antibody titres at protective level and respond to booster vaccination with elevation in titre. Older dogs and cats are able to make primary humoral responses to novel antigens, but the magnitude of these may be reduced relative to titres achieved in younger animals. Fewer investigations have studied the phenomenon of ‘inflammageing’ (the effect of cumulative antigenic exposure and onset of late life inflammatory disease) in these species. Senior cats have increased production of pro-inflammatory cytokines by blood monocytes, but this effect has not been demonstrated with cells derived from older dogs. Numerous studies have investigated whether canine and feline immunosenescence might be slowed or reversed by dietary supplementation with antioxidants, but no significant research has addressed the need for geriatric vaccination protocols.

    HogenEsch H1, Thompson S, Dunham A, Ceddia M, Hayek M. Effect of age on immune parameters and the immune response of dogs to vaccines: a cross-sectional study. Vet Immunol Immunopathol. 2004 Jan;97(1-2):77-85.

    The evaluation of anti-aging intervention strategies in dogs would benefit from reliable quantitative biomarkers of aging. In the present study, the expression of various immune parameters was measured in young and old dogs to identify potential biomarkers of aging. The second goal of the study was to determine the effect of age on the immune response to vaccines. The immune function, including the antibody response to vaccines, was determined in 32 young adult (3.15+/-0.8 years of age) and 33 old dogs (12.1+/-1.3 years of age) of various breeds. Old dogs had a significantly lower lymphocyte proliferative response and a lower percentage of CD4+ T cells and CD45R+/CD4+ T cells, and a higher percentage of CD8+ T cells and a higher concentration of serum and salivary IgA. The most significant differences (P<0.001) occurred in the lymphocyte proliferative responses to ConA and PHA, the CD4:CD8 ratio, and the percentage of CD45R+/CD4+ T cells suggesting that these parameters are potential biomarkers of aging. There was no difference in the percentage of total T and B lymphocytes and the concentration of serum IgM and IgG. Both groups of dogs had protective titers against distemper virus, parvovirus and rabies virus before annual revaccination. The pre-vaccination titer against rabies virus was higher in the old dogs than in the young dogs, and there were no differences in post-vaccination titers against any of the viruses. This suggests that annual vaccination protocols provide adequate protection for old dogs.

    Muirhead TL1, McClure JT, Wichtel JJ, Stryhn H, Frederick Markham RJ, McFarlane D, Lunn DP.The effect of age on serum antibody titers after rabies and influenza vaccination in healthy horses.J Vet Intern Med. 2008 May-Jun;22(3):654-61. doi: 10.1111/j.1939-1676.2008.0091.x. Epub 2008 May 2.

    BACKGROUND:
    The proportion of geriatric horses within the equine population has increased in the past decade, but there is limited information on the immune function of these animals.

    HYPOTHESIS:
    Aged horses will have a lesser increase in serum antibody response to vaccination.

    ANIMALS:
    Thirty-four aged healthy horses (> or = 20 years) and 29 younger adult horses (4-12 years) of various breeds.

    METHODS:
    All horses were vaccinated with vaccines of killed rabies and influenza virus. Horses in each age group were allocated to receive either rabies or influenza booster vaccine 4 weeks after the initial vaccination. Serum samples were taken at 0, 4, 8, and 24 weeks. Rabies serum neutralization titers and equine influenza virus specific antibody sub-isotypes (IgGa, IgGb, IgG(T), and IgA) as well as single radial hemolysis (SRH) titers were determined.

    RESULTS:
    Rabies antibody titers were similar in the 2 age groups at all sampling times. Aged horses had higher IgGa and IgGb influenza antibody titers before vaccination than younger horses but similar titers after vaccination (P= .004 and P= .0027, respectively). Younger horses had significantly greater increases in titer than aged horses at all sampling times for IgGa (P= .001) and at 8 and 24 weeks for IgGb (P= .041 and .01, respectively). There was no detectable serum IgG(T) at any time point. A significant booster vaccine effect was seen for both antirabies and anti-influenza titers. Anti-influenza titer before vaccination also had a significant effect on subsequent antibody response.

    CONCLUSIONS AND CLINICAL IMPORTANCE:
    Healthy aged horses generated a primary immune response to a killed rabies vaccine similar to that of younger adult horses. Aged horses had a significantly reduced anamnestic response to influenza vaccine.

    Muirhead TL1, McClure JT, Wichtel JJ, Stryhn H, Markham RJ, McFarlane D, Lunn DP.The effect of age on the immune response of horses to vaccination. J Comp Pathol. 2010 Jan;142 Suppl 1:S85-90. doi: 10.1016/j.jcpa.2009.10.010. Epub 2009 Dec 1.

    Few studies have investigated immunosenescence in the horse, but it is accepted that the primary and secondary (anamnestic) immune responses may differ between aged and younger horses. The aim of the present study was to determine whether aged horses have a protective immune response post-vaccination. Thirty-four aged healthy horses (> or =20 years) and 29 younger adult horses (4-12 years) of various breeds were vaccinated with commercially produced killed rabies and influenza vaccines. Rabies serum neutralizing antibody titres and equine influenza virus specific antibody subclasses (immunoglobulin IgGa and IgGb) and single radial haemolysis titres were determined. Healthy aged horses mounted a primary immune response to rabies vaccine that was similar to that of younger adult horses. However, aged horses had a significantly reduced anamnestic response to influenza vaccination in comparison with the younger adult horses, even though the pre-vaccination antibody titres of aged horses were higher. Rabies antibody titres in both groups declined significantly by 6 months post-vaccination. Serum concentrations of selenium (Se) and vitamin E were measured to test for potential confounding effects. Significant numbers of horses had suboptimal serum Se concentrations, but Se status had no significant impact on antibody production after vaccination.

    HogenEsch H1, Thompson S.Effect of ageing on the immune response of dogs to vaccines.J Comp Pathol. 2010 Jan;142 Suppl 1:S74-7. doi: 10.1016/j.jcpa.2009.09.006. Epub 2009 Nov 7.

    Ageing is associated with a decline in functional competence of the immune system, sometimes referred to as immunosenescence. As this increases the susceptibility of dogs to infectious diseases, it is important to determine if the efficacy of vaccines is affected by ageing. Studies to date suggest that the primary response to vaccines may be compromised in old dogs, but recall responses remain intact. Information on the effect of ageing on the duration of protective immunity following vaccination is needed.

  7. lorac says:

    Interesting data for dogs and horses. Something that I’ve wondered about in humans with respect to immunosenescence is the type of vaccine and robustness of antibody response. As you may know, human babies don’t mount very good responses to killed organism vaccines. yet, vaccines that use an antigen coupled with a carrier work will. The example that comes to mind is a vaccine to Hemophilus influenza, which causes meningitis. The vaccine used now is a conjugate vaccine and works in babies less than 18 mo. Many vaccines are killed organism type. Perhaps a conjugate vaccine would be better for elderly too. This is pure hypothesis on my part. I don’t work in immunology field any more, and maybe the studies have been done to see if a different type of vaccine could “overcome” immunosenescence.

    I may start doing titer tests for my dog before immunizing. False positives are the concern, because i would opt for re-vaccination if there were a negative.

    Thank you again for bringing sanity and science to veterinary practice and sharing it.

  8. Rebecca Rice says:

    Thank you for this very helpful post. However, can you clarify a few things?

    From what you have written, it appears that sometimes a high antibody level isn’t necessarily a guarantee that a dog is immune to an illness, and low level isn’t an indicator that the dog is NOT immune. And, in your follow-up, you clarify that you prefer doing 5-year boosters, and that therefore, the number of vaccinations that will be skipped by doing titers instead is relatively low, and that doing titers might actually cause someone to potentially over-vaccinate a dog, due to the “low numbers does not necessarily mean not immune” situation. I can understand all of that.

    What about the flip side? If the entire purpose of vaccinating is to increase the number of antibodies in the blood stream, then why would it be considered acceptable to do 5-year boosters on a dog that demonstrates low antibody levels before then? I guess what I am trying to figure out is why doing vaccinations on a time schedule is any better than titering, if there is such a wide discrepancy in the protective value number of titers. Yes, most dogs may be protected at 5-7 years after showing an initial response, but how do I know that MY dog is, if it seems that the titer results don’t really matter? Why should I trust 5 years, and not 3 or 7 or 2? I don’t particularly want to try and infect my dog just to be sure that she is still protected, but if I can’t trust the titers, then it seems like I am back to going on blind faith based on some arbitrary timeline.

    Can you clarify what is different between the two approaches?

  9. skeptvet says:

    As you can see, it’s a complicated subject. 🙂

    In general, a HIGH antibody titer does mean a dog is protected for those diseases in which the antibody titer and protection correlate, which is most of the common ones we vaccinate for (parvo, distemper, and rabies). There are some diseases in which a high titer does not necessarily mean the dog is protected, but for the usual things we are vaccinating against in dogs, a high titer is very strong evidence of protection, so additional vaccination would be unnecessary.

    A low titer, however, tells us nothing about a dog’s susceptibility to a disease. There are other aspects of the immune system besides antibodies which are primed to defend against a disease, and these can be enough to protect a dog even if titers are low. The purpose of vaccination, is to prepare the immune system to protect against an infectious organism, and this involves lots of things besides antibodies, which are only one measure of protection.

    If we vaccinate everybody on a schedule, we know that some percentage of dogs will be adequately protected for the whole interval (the exact number varies by disease and vaccine but is usually over 90%). We also know that some of these dogs will receive unnecessary vaccinations in the sense that they are already protected when vaccinated. This is not a big deal because the “extra” vaccines are very unlikely to cause harm. We don’t want to wait until a dog is vulnerable to a disease before vaccinating it, because that leaves a window open for them to get the disease. We also don’t want to give a lot of unnecessary vaccines, and the 5-7 year schedule is a reasonable compromise.

    Finally, we also know that a very tiny proportion of dogs won’t get effective immunity no matter how much vaccine they receive. These dogs are protected indirectly by herd immunity if we properly vaccinate the rest of the population, but they can’t be directly protected by vaccination because such “non-responders” don’t react to vaccines in the usual way. There is, unfortunately, no test we can use to identify these individuals definitively, though sometimes we can spot them if we check titers after vaccinating and they fail to mount a response from the start.

    So as far as making decisions for your own individual dog, there is no way to be 100% certain that he or she is protected and doesn’t need a booster vaccination. High titers are a very good indicator that a vaccine is not necessary. Likewise, the recommended booster intervals are reliable for the vast majority of dogs (the same is true for humans, which is why we rarely have titers for the many things we get vaccinated against). Doing a titer annually or at some point earlier than the recommended booster interval could have several outcomes:
    1. High titer- Your dog is almost certainly protected, and no vaccine is needed. Doing this test was probably unnecessary, but harmless and perhaps it reassures you.
    2. Low titer- Your dog is likely protected since we’re within the recommended interval for boosters, but the test doesn’t tell us one way or another. You can choose to vaccinate, which is unlikely to do harm and which may or may not add protection (there really is no way to know). Or you could choose not to vaccinate, though again there is no other way to know if your dog is at risk. Or, there is a very tiny chance your dog could have low titers because it is a non-responder who doesn’t get protection from vaccination. In this case, vaccination won’t help directly, but again there is no way to confirm this with certainty.

    SO as I said in the article, I don’t think titers themselves do any harm, but they don’t provide us with much actionable information. Sure, fi they are high we can relax and skip the vaccine. But otherwise, we are guessing about the dog’s status, and our decisions about giving or not giving the vaccine are no more likely to be the right decision than if we hadn’t done the test.

    Does this help at all?

  10. bryan flake says:

    I’ve never heard of an immunization explained quite the way that you explained it. What an interesting idea that the cells in the body examine and study what is contaminating everything and then come up with a proactive remedy to fight it better next time. I understood this idea before today. However, the way you illustrated it in reference to dog vaccines is really clear to me.

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  12. Jane Dee says:

    A very interesting read. I am in the process of deciding what to do with my youngest dog (14 months). I had both my poodles titre tested, the 2 1/2 year old levels showed a high positive but for the pup, all measurements indicated a low positive. Do I booster her or rely on the fact that any immunity is immunity and trust the memory cells to do their jobs. I can’t discuss this with my vet because she is ‘old school’ 100% annual vaccinations 🙁

  13. skeptvet says:

    The existing evidence suggests pretty reliable protection from 3-5 years for most dogs, so I tend to recommend boosters at this interval. Again, if the titer is high then you can skip the booster, but if it is low then it doesn’t really tell you anything about protection. Also, worth bearing in mon that the risks of the vaccines are extremely low.

    Good luck.

  14. Ulrike Godey says:

    This was interesting reading.

    We moved from Ireland to Spain in 2013 and after 18 months here without any problems one of our labradors had an episode of paralysis September 2014 which was diagnosed as idiopathic polyradiculoneuritis. The dog was 6 years old at the time and had been vaccinated against rabies every three ears after initial immunity was established through titer testing in 2010. Unless I am mistaken polyradiculoneuritis is an autoimmune issue, and thus we were advised not to vaccinate her at all for the next two years, even though her episode was not after any vaccination. Thankfully, the dog recovered 90%, but seems to have smaller , less extreme episodes every year since then. The problem is that we do need to travel quite a bit due to family living in other parts of Europe, and we usually take the dogs with us in the car. The last rabies vaccination ceased to be valid in November 2015. We had did a rabies antibody titer in March 2016 (the blood was sent to an approved laboratory in Germany by the vet here in Spain), and the result is shows that she has a titer =>6.01 IU/ml , when according to the WHO/O.I.E recommendations a titer of above or equal 0.5 UI/ml after vaccination is considered to provide sufficient protection and allows travelling under the terms of Pet travel scheme (PETS) and EU regulation. The dog was last vaccinated in 2012. Now, my dilemma really is whether to vaccinate the dog again, or not. Her immune system is compromised, she has never been quite the same since before her paralysis, but nearly. She is happy and lively and the illness seems to be unconnected to any vaccines. But I assume that the risk is higher for her than for ‘normal’ dogs, and as she already has a high titer I am worried that another dose of vaccine will play havoc with her immune system. But legally we cannot take her to another country because she has no valid rabies jab, despite having a titer well above the required value, four years after the last vaccination. Any advice as to risks versus benefits of vaccinating her against rabies again would be greatly appreciated. (The province we live in is one of the very few in Spain that does not require dogs to have rabies vaccination, most other provinces require annual or even biannual vaccinations by law, not sure what would happen then with our dog!)
    Thanks a lot in advance!!

  15. skeptvet says:

    There is, of course, no clear and direct evidence that can answer your question. I will say, though, that the idea that animals with a history of autoimmune disease are at greater risk of recurrence or other negative effects from vaccination has never actually been shown to be true. Even the evidence showing vaccines as one possible trigger for autoimmune disease is weak, and certainly less conclusive than the link between infectious disease and autoimmune disease. Considering that our immune system is exposed to far more stimulation from normal living than from occasional vaccination, vaccines seem to be a pretty small contribution to the overall stimulus our immune system must deal with. Some calculations show that the entire childhood vaccine series adds up to about a week of exposure from everyday life.

    So while there is no clear evidence either way, I think the fears about vaccine and autoimmune disease are exaggerated and extrapolated from weak evidence. I agree that a booster would be unnecessary given the presence of a protective titer, and it is good medical practice not to give unnecessary treatments. But I also think the risk is low, though ultimately unpredictable.

    Good luck!

  16. Jennifer Robinson says:

    I’ve recently hit another disadvantage of titer testing. I’m moving to New Zealand, and NZ has strict controls to keep rabies from getting established. So my dogs have had to do rabies titer tests through Kansas State University. KSU is expensive and slow. I can get a rabies vaccination done for $25 and it’s over and done with for three years. The vet charged me $160 for the titer and $77 for shipping. It was three weeks before results came back.
    Unfortunately for me, and consistent with results you reprinted above, the two older dogs (6 and 12 years) were fine, but the younger dog (3 years), who was accidentally given two booster shots two years ago, titered out at 0.29 IU/ml, thus failing the test, requiring another round of vaccination and testing, and delaying my departure by at least another month. I wish I had ignored advice to avoid ‘unnecessary vaccinations’.

  17. skeptvet says:

    Thanks for the feedback. I do a lot of health certificates for travel to NZ and Australia, and it is quite a project! Obviously, they want to keep rabies out, so the intent is worthwhile, but it’s hard on people travelling. And you are quite right that the relationship between titers and vaccination is much more complicated and unpredictable than vaccine opponents often make it seem.

  18. Angela B says:

    We recently had a 10 week old puppy die from parvo. We found another puppy to adopt whose owner is willing to keep him until he has completed his series of puppy shots. (Due to our yard being contaminated) Will a parvo titer done on him after his 3rd shot (received @ 17 weeks) be accurate to assure us of his safety? Or a titer after his 4th shot at 20 weeks?

  19. skeptvet says:

    As long as he has two vaccinations after 12 weeks of age (usually given at 12 weeks and 16 weeks), he will very likely be protected. An additional vaccination at 20 weeks may not be necessary, and a positive titer will certainly indicate a protective response, so if you have a titer done 2 weeks after his final vaccination (at 16 weeks), that should tell you if he is adequately protected.

  20. Serena Ferrario says:

    Hello, first of all thank you for this informative and insightful piece!
    As many pet owners, I’m quite concerned about the risks of over-vaccination, especially for elderly cats and dogs. I’ve seen that you have discussed the concept of immunosenescence above, but not having any specific background in veterinary medicine and immunology, I didn’t understand all the implications and, most of all, I can’t make up my mind whether titer testing would offer a reliable alternative to the annual vaccination programme for my aging cats and whether the fact that have been immunized yearly for 6/7 years (both for core vaccinations, which here in Italy are FCV, FHV and FPV, and for leukemia) can offer an extra or longer lasting protection against diseases in the future, or if, based on the expectable decline of their immune response, their vaccination schedule should be mantained as before (every year) or even intensified. On the other hand I’m afraid that a prolonged and unnecessary overstimulation of their immune system might result in an abnormal inflammatory reaction and lead or hasten the onset of chronic illnesses such as CRF or others, but once again I cannot tell if this is an actual risk or something that has been blown out of proportion by those veterinarians who strongly adverse vaccinations (and I can’t understand why).
    Talking to my own vet, I was told that 1) yes, an yearly vaccination may be excessive, but this gives them the chance to check the pets general condition (???), 2) while the chore vaccinations could be delayed every two years, the shots for leukemia have to be administered every year or they will be ineffective. Now, are there, to your knowledge, scientific data or articles supporting the necessity to repeat the immunisation for Felv annually regardless of the cat’s age or would it be advisable to check their antibodies titer before repeating the vaccination?
    Many thanks in advance!

  21. skeptvet says:

    There are few absolutes in medicine, and of course the particular risks your cats face and the vaccines in common use where you live may differ from where I am, so hard and fast rules are usually not a good idea. I will say that it is widely accepted and well-established that yearly boosters for core vaccines in cats are unnecessary. Whether they increase the risk of disease is not as clear, however I am a proponent of not doing unnecessary things to patients, so I do not recommend annual FHV/FCV/FPV vaccines. Boosters every 3-5 years are more reasonable, and it may be appropriate not to vaccinate for some diseases (e.g. FPV and FeLV) at all after 8-10 years of age. For indoor only cats with no exposure to cats outside the household, a strong argument can be made for the initial kitten series and 1-year booster followed by no additional vaccinations, so we do have to consider exposure risk and lifestyle in making vaccination decisions.

    The FeLV vaccine is an example of this. FeLV does need to be given annually if the Purevax vaccine is used (and I do not recommend the adjuvanted 3-yr vaccine due to a probable increased risk of fibrosarcomas). However, whether or not a cat is vaccinated for FeLV depends on its exposure risk. Infection requires regular, close exposure to infected cats, so only cats going outdoors or living with an infected cat are at high risk and are routinely vaccinated here. And susceptibility seems to decline markedly with age, so often the vaccine is not given after 8-10 years of age.

    I think an annual visit is reasonable, but I don’t believe we need to require unnecessary vaccinations in order to get clients to bring their pets in for this. That was an early fear expressed by many vets when it was first proposed to extend vaccination intervals. However, many vets have stopped giving annual boosters and still see their patients regularly for wellness examinations, so I’m not convinced by this argument.

    I have written another post specifically discussing current vaccination guidelines, and this one may be more useful to you than the post on titer testing:

    Routine Vaccinations for Dogs and Cats

    I hope this helps!

  22. Angela B says:

    Continuing from my question above (thank you for the quick response), the AAHA guidelines state that a modified live virus given for CPV will provide immunity “usually” within 3-5 days (where there is no maternal antibody interference.) Is this true? What is the reasoning for waiting 2 or more weeks after this last vaccination to perform a CPV titer? If we opt for the 20 week shot, would we need to wait another 2 weeks before bringing him home safely?

  23. art malernee dvm says:

    I think an annual visit is reasonable,

    not in a profession that tells itself that annual revaccination is not needed but it gets the patient back every year. How is that reasonable? I have not seen any pet records in Florida where the vet was not vaccinating annually for something. If the profession is going to give the pet something it does not need that makes the annual visit unreasonable in my mind.

  24. skeptvet says:

    Antibodies are only one element of immune function, which is why a pet can be protected against infection even without measurably protective antibody levels. What’s called cell-mediated immunity also plays a role, and we don’t have an easy way to measure this. With a modified live or “infectious” vaccine, onset of immunity is more rapid than antibody production. However, since antibody levels are the only reliable way to assess immunity, we have to wait for those levels to go up before we can be sure the vaccine has been effective in generating protective immunity. Waiting 2 weeks may not be necessary, but there is no way to know if a dog is protected before the titer rises, so it is safest to wait for this.

  25. skeptvet says:

    You don’t seem to have understood my comment, Art. I believe an annual visit, involving a thorough history and physical examination, is reasonable because owners do not always notice improtant signs of disease that veterinarians may detect. There is no solid evidence that such visits reduce morbidity and mortality in veterinary patients, so the benefits are unproven, but it is plausible that such benefits may exist, and the cost and risks are low.

    An annual visit, however, does not require annual vaccinations. I see most of my clients annually regardless of whether or not any vaccinations are needed, as do the other 29 doctors working at my practice. While some vets see annual vaccines as a way of getting people in for a visit, I think that is an outdated and unjustifiable strategy. However, just because annual boosters are not necessary doesn’t mean we shouldn’t encourage people to bring their pets in for evaluation regularly.

  26. Angela B says:

    If the “onset of immunity is more rapid than antibody production,” then what is the difference between the two?

  27. skeptvet says:

    Well, as I said the immune system is complex, and there are many ways it fights infections. Antibodies are one tool to fight infection, but there are lots of others. Antibodies can be easily measured, but most of the other tools that fight infection can’t. So a high antibody level can tell us a dog is protected from certain diseases (those for which antibodies are the main tool the immune system uses). But a low antibody level doesn’t necessarily mean the dog is susceptible because the others tools might still prevent the infection. So “onset of immunity” means the point at which the dog is safe from infection. Antibodies take longer to get going than some of the other elements of the immune system, so sometimes a dog is protected even before the antibody levels have gone up. The problem is we can’t know this for sure in most cases because we can’t measure these other elements.

    In the case of CPV, since a modified live vaccine is used, tools other than antibodies get activated right away, which is why dogs can be protected before the antibody levels are high.

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