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Kansas State Veterinary Diagnostic Laboratory

Dog and Cat Vaccines and Titer Testing

By Susan C. Nelson and Susan M. Moore

The number of booster vaccines our pets receive is becoming more commonly discussed amongst both pet owners and veterinarians. Those in opposition of vaccines are passionate about their views, while those in favor of vaccines are equally passionate on the subject. Is one side right and the other wrong, or is there common ground to be found? A little of both. Not all is known about the immune system and much research still needs to be done. Additionally, there is misinformation on the internet, as well as sensationalized stories about pets who may, or may not, have experienced a vaccine reaction. 

Vaccines were developed to help prevent infectious disease, and they do. Vaccine technology has advanced tremendously since the inception of vaccinology. Over the years, veterinarians have seen fewer vaccine-related issues than previously reported. Vaccine opponents often argue that ingredients such as adjuvants (aluminum, mercury, formaldehyde and foreign proteins) are often the source of reactions. This was true in the past, however many vaccine have been “purified” over the years, meaning extraneous proteins have been removed. Some of the aforementioned adjuvants have been entirely discontinued in the production of vaccines. This has made them much less reactive for our patients.

Click here for more information on specific vaccines, including rabies, and protection...

A good example of a vaccine that has become less reactive over the years is the leptospirosis vaccine for dogs. This vaccine was much more reactive when it was first developed years ago. The number of dogs who have adverse reactions to this vaccine are now minimal; yet every year veterinarians treat many dogs that have not been vaccinated against leptospirosis, a disease that can cause liver and kidney failure… and is contagious to people as well. Some of the more recent outbreaks were in urban areas where the bacteria was acquired from contact with urine of infected rodents.

Another vaccine commonly in question is the Canine Distemper vaccine for dogs. Nobody can argue that this is often a fatal disease for dogs. There are cases of post-vaccine encephalitis seen from the use of attenuated (contain weakened live virus) distemper vaccines; however, these are rare and veterinarians see far greater numbers of distemper in unvaccinated dogs then they see post-vaccine encephalitis. Every year there are reports of large outbreaks in shelters and communities in dogs who have not been vaccinated against this disease. Lastly, there is a recombinant distemper vaccine available that does not cause vaccine-induced encephalitis for those that are fearful of using the attenuated vaccines.

Canine parvovirus (aka. parvo) leads to the death of numerous dogs each year; many of these puppies. Most of these deaths could be prevented if the dogs had been properly immunized. Some vaccine opponents state that even vaccinated dogs get diseases such as parvo. This is partially true in that no vaccine is 100% effective due to individual responses to vaccines. There are some animals that are considered “non-responders” and will not ever develop immunity in response to vaccination. If one looks at the vaccine history for the majority of “vaccinated” dogs who contract parvo, it will be found that they never completed their vaccine series as a puppy or were never vaccinated. Why this happens is that puppies have antibodies to the virus given to them from their mothers (aka. maternal antibodies) and as long as these antibodies are active in their system, they will block the puppy’s immune response to the vaccine given at that time. For example, if the maternal antibodies were active during the first puppy vaccine given at 6-8 weeks of age, and the puppy received no further vaccines, the puppy will have no immunity once the maternal antibodies go away and thus becomes susceptible to developing the disease when exposed to the virus. This is not a vaccine failure, but failure to have the puppy properly vaccinated.

Let’s not forget the cats. Feline Parvovirus (aka. Feline distemper) is very similar to its canine counterpart in that is also very common and deadly. It is rare in properly vaccinated cats. Maternal antibodies can interfere with this vaccine as well, so an appropriate vaccine series is necessary for protection.

Feline leukemia virus is a very contagious and deadly virus for cats that was commonly seen many years ago. It is now seen in much lower numbers since the vaccine came out in the 1980’s, even though the vaccine is not considered 100% effective.

Rabies is a deadly virus for all warm-blooded animals, including our cats and dogs. It is also able to be transmitted to people as well. Over 55,000 people die from rabies each year, with many of them being children1. Most of these are due to bites from infected dogs. The number of people who die from rabies in the US is substantially lower, and those who contract it in the US have usually acquired it from a bat exposure2

One statistic that is often left out of the rabies vaccine debate is that there has been a reduction in laboratory-confirmed cases of rabies among dogs in the United States from 6,949 cases in 1947 to 58 cases in 20163. Many of these were due to the dog variant of rabies. In the US, the dog variant of rabies does not exist anymore due to laws that mandate the vaccine for dogs. This does not mean that dogs cannot contract rabies, however, as they can still obtain it from skunks, raccoons, bats, etc., and then become a risk to humans and other animals.4

For many years now there are more reports of rabid cats than dogs in the US as many places do not have laws requiring cats to be vaccinated. Lastly, most cases of rabies in the US involving domestic animals are animals that were never vaccinated against rabies or were overdue on their vaccine boosters.

What about the flip side of the argument? Can vaccines be harmful for some pets? While adverse reactions to vaccination can occur in many species, the rate of these reactions is low. The risk of not having immunity to common infectious organisms far outweighs the risk of developing serious illness as a result of vaccination.

Click here for more information on adverse reactions to vaccines...

One study in Canada that was done regarding adverse reactions to vaccination in dogs and cats reported the Canadian Food Inspection Agency’s (CFIA) Canadian Centre for Veterinary Biologics (CCVB) between January 1, 2010 and June 30, 2014 showed this:

Allergic reactions represent the most common type of SAE (Serious Adverse Event) reported with 2.663, 0.187, and 2.646 probable, possible, or unknown events per 10,000 doses of canine, feline, and rabies vaccines respectively.

Another study by Moore et al reported a total SAE rate of 13 reports per 10,000 vaccinated dogs in their large-scale (1,226,159 dogs) Banfield Hospital surveillance study. This is a less than a 1% reaction rate.5

A flaw in these studies is that not all adverse events get reported, and some reactions may get reported as some other type of condition. However, one has to be aware that a temporal association between vaccination and the development of a clinical sign does not necessarily equate to a cause and effect relationship between the vaccine and the illness. There can often be many other physical and/or behavioral issues occurring around the timespan when vaccines are given. An example of this would be a dog who receives a vaccine and develops vomiting and diarrhea a few hours later. This could be due to the vaccine or it may also have been due to dietary indiscretion that was caused from getting into the garbage earlier that day. 

There are some disease conditions or situations where vaccines may not be in the best interest of a patient. For example, owners of animals that have experienced severe, adverse reactions to vaccines, animals with impaired immunity, and patients undergoing some cancer treatments, should discuss vaccination with their veterinarian. So what can one do if this is the case for their pet?

  • Reassess lifestyle to determine essential vaccines.

  • Allow longer intervals between core vaccine doses after completing an initial series.  

  • Separate vaccine administration by at least 3 weeks if an adverse reaction was previously seen when multiple vaccines were given on the same day. 

  • Pre-medicate with Benadryl +/- a dose of corticosteroid in the case of more significant reactions.

  • Administer a different brand of vaccine for the next scheduled booster.

  • Check vaccine titer for some diseases to see if the vaccine is necessary.

Vaccine titers have been gaining more acceptance over the past few years to reduce the frequency of vaccination. In order to be useful, two criteria need to be met: 1) One needs to be able to detect a measurable immunity (antibody) to a disease in a blood sample, and 2) There needs to have been challenge studies performed to associate protection with that specific titer level. A challenge study shows that animals which have a specified antibody titer did not get sick when exposed to the disease for which the titer was checked.

Vaccine titers are not an effective means for assessing protection for some diseases. In general, these are for the diseases included in the noncore vaccine category as their specific protective level of antibodies have not been determined. Noncore vaccines are also known as life-style vaccines, and administered based on risk determined by geographic location and activities. For dogs, leptospirosis, Lyme, Bordetella, parainfluenza and canine influenza are risk-based vaccines. For cats, FeLV, Chlamydophila (chlamydia) and Bordetella are administered to cats with greater risk of exposure.

Vaccine titers can be useful for determining the need for DA2P (Canine Distemper, Adenovirus and Parvovirus) and FVRCP (Feline Rhinotracheitis, Calicivirus and Panleukopenia) boosters. These are core vaccines. Every animal should receive core vaccines due to the wide-spread prevalence and severity of the diseases that they prevent. After the pet has completed their initial series of these vaccines and boosters one year later, annual titers can be determined thereafter to assess the need for continued boosters. Many cats and dogs have titers to these diseases lasting many years. In fact, several years ago the AVMA and AAHA recommended increasingthe vaccine interval for DA2P and FVRCP from 1 year to 3 years based on titer testing results.

However, titers have also detected patients that needed their boosters sooner than every 3 years as well, so they are useful in detecting the need for boosters for both animals that don’t need vaccination as well as those that do. Titers are checked by obtaining a blood sample and submitting it for testing. Titer testing can also be considered at the end of the initial series to ensure the patient mounted a protective immune response to the vaccine.

Rabies is a core vaccine and titers can be determined, but the use of titers in lieu of rabies vaccination is not as straight forward. Rabies vaccination is required for dogs (and often cats as well) in most states and/or municipalities as part of rabies control and prevention policies. Rabies is zoonotic (can be transmitted to people) and control in rabies vectors (animals that can carry the virus and infect others) is the most efficient method in prevention human rabies deaths. These laws currently do not include the use of titers in place of vaccination. The other complicating factor is that there is no agreed standard titer value that is considered protective. Not all laboratories that determine titers are accredited and not all test methods are accurate. For a disease that has such great significance with regards to public health, it is important to use a lab that is accredited and has quality control measures in place.

Click here for more information on evidence of rabies antibody levels and protection...

Peer-reviewed publications examining rabies vaccine protection through challenge studies provide the best information on what level of circulating rabies antibody is correlated with protection from clinical rabies. Challenge is often performed via the intracerebral route so represents an extreme challenge route of exposure for pets. Many of these studies have used the mouse neutralization test (MNT) or the rapid fluorescent focus inhibition test (RFFIT) for measurement of antibodies. In summary, we find from review of these papers that currently vaccinated dogs and cats with rabies antibody levels above 0.5 IU/mL survive more frequently than dogs and cats with levels below 0.5 IU/mL6,7However, there have been reported the rare animal succumbing to challenge with a level above 0.5 IU/mL so the correlation is not perfect. The probability of survival increases with higher IU/mL values up to around 1.0 IU/mL, meaning animal with a level of 1.0 IU/mL has a good a probability of survival as animal with a level of 10.0 IU/mL. This correlation of protection has been found to be similar in several species8.

There are very limited published data on dogs and cats out-of-date for their rabies vaccination and survival from challenge. One paper looking at dogs, 5 years, and cats, 4 year, post-vaccination showed fair correlation of rabies antibody level and survival from challenge with 54% of dogs and 87% of cats with detectable rabies antibody just before challenge; and 92% of dogs and 100% of cats surviving9.

The challenge studies also show the timing of the blood draw is important is predicting survival, as is evidenced in the out-of-date vaccination study above. Correlation is best if the time-period from vaccination to titer check is earlier rather than later after vaccination with the peak period at 21 to 30 days post vaccination8.

Review of the published studies pointed up the difficult in comparing rabies serology between studies if the same laboratory test method and cut-off level was not used8

The above findings emphasize that if rabies titer testing can be used in lieu of vaccination, a number of standards will need to be established: level of rabies antibody, timing of blood draw after vaccination, approved test method are the most important.

Some states are starting to consider laws in support of the use of titers in those animals that have experienced severe adverse reactions to vaccines or have other health issues that would preclude vaccination. These states still require the vaccine in normal circumstances, however. One can lobby for more research to be done in this area and support funding so we may, in the future, have better insight into the use of titers in lieu of this vaccine.

The bottom line is vaccination is safe for the majority of pets and vaccines save many more lives than they harm. What can you do if you are still concerned about over vaccination? 

  • Speak with your veterinarian about extending the duration of core vaccines to 3 years as per AAHA, AVMA and NASPHV Compendium of Animal Rabies Prevention and Control guidelines.

  • Consider checking annual titers for FVRCP in cats and DA2P in dogs.

  • Review life style risks for your pet.

References:

  1. Organization WH. WHO Expert Consultation on Rabies, third report. In. Geneva: World Health Organization; 2018:1 - 195.
  2. Prevention CfDCa. Human Rabies Prevention - United States, 2008 Recommendatoins of the Advisory Committee On Immunization Practices. Atlanta, GA 2008 2008. Vol. 57/RR-3.
  3. Ma X, Monroe BP, Cleaton JM, et al. Rabies surveillance in the United States during 2016. J Am Vet Med Assoc. 2018;252(8):945-957.
  4. Velasco-Villa A, Mauldin MR, Shi M, et al. The history of rabies in the Western Hemisphere. Antiviral Res. 2017;146:221-232.
  5. Moore GE, Glickman NW, Ward MP, Engler KS, Lewis HB, Glickman LT. Incidence of and risk factors for adverse events associated with distemper and rabies vaccine administration in ferrets. J Am Vet Med Assoc. 2005;226(6):909-912.
  6. Bunn TO, Ridpath HD. The relationship between rabies antibody titers in dogs and cats and protection from challenge. U S Department of Health, Education and Welfare, Public Health. 1984(11):43-45.
  7. Aubert MF. Practical significance of rabies antibodies in cats and dogs. Rev Sci Tech. 1992;11(3):735-760.
  8. Moore SMG, A.; Vos, A.; Freuling, C.M.; Ellis, C.; Kliemt, J.; Muller, T. Rabies Virus Antibodies from Oral Vaccination as a Correlate of Protection against Lethal Infection in Wildlife. Tropical Medicine and Infectious Disease. 2017;2(31).
  9. Lawson KF, Crawley JF. The ERA strain of rabies vaccine. Can J Comp Med. 1972;36(4):339-344.