Antibody Titers vs. Annual Vaccination  
Richard B. Ford, DVM, MS  
Professor of Medicine  
Diplomate ACVIM and (Hon) ACVPM  
North Carolina State University

Is it feasible to perform annual antibody titers in patients rather than subject them to annual booster vaccination?  Many of the discussions on vaccination protocols today quickly turn to the concern over use of antibody titers as a means of assessing immune status, rather than subject the patient to an annual booster.  Despite the fact that a growing number of laboratories offer selected canine and feline antibody titers to veterinarians, there are a number of significant factors that, in this author’s opinion, do NOT justify offering this service to clientele on a routine basis.  Consider the facts: 

FIRST:  IT’S IMPORTANT TO NOTE…serum antibody titer to a particular antigen, especially a virus, is a relatively crude laboratory method of assessing immunity.   Remember:  antibody concentration is not necessarily synonymous with immunity.  While a “POSITIVE” titer to canine distemper, canine parvovirus, and feline panleukopenia generally correlates with protection, a “NEGATIVE” titer to these antigens does not necessarily correlate with susceptibility. The need to vaccinate a patient with a NEGATIVE titer may not be necessary since cell-mediated immunity, in the principle immune response required to prevent disease. [1]

SECOND: standardized laboratory methods for determining antibody concentration in serum for the various vaccine antigens has not been established in the US.  Therefore, results reported by one lab can be (and are!) substantially different from those reported by another.  Comparing test results between laboratories is not possible.  NOTE:  most diagnostic laboratories report classic titers, in which 2-fold dilution of serum are made,,,the highest dilution that gives a positive test result is reported.  Using the 2-fold dilution technique, the amount of error is approximately a 4-fold dilution.  

THIRD: titers are currently available only for canine distemper, canine parvovirus, and feline panleukopenia.  Testing is not routinely available for most of the other vaccines currently on the market.  While it may be possible to develop a laboratory test to measure one or more types of antibody to a particular pathogen, the correlation between antibody titer and protection is so poor (or non-existent) that test results are meaningless (e.g., feline leukemia antibody, canine coronavirus, feline coronavirus).

There’s yet another rather basic issue that argues against routine use of antibody titers to determine whether or not an individual patient should be vaccinated.  The more that veterinarians do use a reputable laboratory to perform antibody titers on individual patients the sooner it will become apparent that titers do, in fact, persist for several months and that continued testing is quite unnecessary.  Excellent studies recently published support this.

The 2006 AAHA Canine Vaccination Guidelines have included additional information pertaining to the application, what little of it there is, of antibody titers in clinical practice.  In summary, antibody titers can be used to:

A.  To assess response to the initial series of puppy/kitten vaccinations…testing should only be done at 12 weeks or older to assure lack of interference by maternal antibody.  The sample should be collected 2 or more weeks following the last vaccination.  IF the titer is negative (“non-responder”) then the animal should be re-vaccinated using a different product.  That may, or may not, immunize the patient.

B.  The “I don’t trust the Guidelines” rationale:  substituting Antibody titers for annual vaccination is perhaps the most common reason veterinarians submit serum for vaccine antibody titers.  This is, however, a ‘self-fulfilling’ venture…eventually, it becomes apparent that most or all patients will have a protective antibody titer at 1 year, 2 years, and 3 years post vaccination. 

C.  Dobermans and Rottweillers are immune deficient.  Actually, they’re not.  Today, the numbers of non-responders in the general dog population is not different from these 2 breeds.

D.  Measuring Antibody response to natural infection in recovered dogs/cats. 

E.  Rabies titers are also available from only from either of 2 certificated laboratories in the US (Kansas State University-Rabies Laboratory) and the USDA’s Animal Disease Diagnostic Laboratory in Ames Iowa.  These are not used to validate vaccination…they are used to prove immunization status prior to transporting dogs/cats out of the continental US.  Hawaii and selected countries outside the US accept titer results as proof of immunization/protection.

 

Feline Vaccine-Associated Sarcoma  
The Case Against Adjuvant  

Richard B. Ford, DVM, MS  
Professor of Medicine  
Diplomate ACVIM and (Hon) ACVPM  
North Carolina State University

In 1999, the American Association of Feline Practitioners (AAFP) sponsored an Advisory Group of veterinarians to review available literature on feline vaccines and develop a set of Guidelines to facilitate efforts by veterinarians to implement rational vaccination protocols.  In January 2000, that Advisory Group published the 2nd iteration of the AAFP Feline Vaccination Guidelines.  In 2003, the American Animal Hospital Association (AAHA) sponsored the Canine Vaccine Task Force that developed vaccination Guidelines for the dog.  Both groups have recently reconvened and will publish updates early in 2006.  All of this activity has had significant impact in clinical practice as veterinarians are being challenged to provide comprehensive ‘wellness programs’ yet deal with significantly unfamiliar vaccination guidelines, particularly those recommending a 3-year booster interval for adult dogs and cats vs. customary annual booster vaccination. 

Still today, the feline and canine vaccination Guidelines are not without controversy.  In fact, one of the fundamental controversies behind the decision to develop Feline Vaccination Guidelines was the fact that, by 1999, it had become well established that routine administration of vaccine to cats, particularly FeLV and Rabies vaccines, resulted in the development of an aggressive, malignant sarcoma in some cats.  In 1993, the prevalence of tumor formation was estimated to be 1 to 2 cats affected for every 10,000 vaccinated.  Today, 15 years later, that estimate of prevalence remains virtually unchanged.  Recent estimates are that between 1 in 10,000 and 1 in 3,000 cats will develop a tumor directly related to vaccine administration. 

Despite the efforts of several research groups to identify the underlying cause of what is now called “Vaccine-Associated Sarcoma” (VAS), most of the literature on affected cats continues to deal with treatment, rather than prevention.  Ironically, in 2001, the AVMA’s Vaccine-Associated Feline Sarcoma Task Force published recommendations to administer FeLV vaccine in the LEFT rear leg, as distally as possible while recommending that rabies vaccine be administered in the RIGHT rear leg as distally as possible.  The reason…if/when a tumor develops, the leg can be amputated!   

This is hardly an acceptable solution to what is now recognized as the most significant adverse event associated with feline vaccination…and the ultimate question regarding VAS remains…  

What can be done to mitigate the risk of VAS in cats? Today, available research provides no definitive answer to this question. However…there exists a body of literature that implicates a link between the administration of adjuvanted vaccine…chronic inflammation induced by vaccine adjuvant…and tumor formation. That evidence is summarized below:

First…it’s a cat thing!  VAS has been reported in humans and in dogs…but documented cases are exceptionally rare compared to the VAS prevalence recognized in cats.  Yet…it’s not just vaccine.  There are published reports documenting fibrosarcoma formation in cats that were caused by ocular trauma, repository drug administration, and nylon suture left in skin for an extended time.  Interestingly, in July 2004, investigators at the University of Minnesota reported having identified an allele in cats that were predisposed to develop VAS (a commercial test is pending).

Second…it was 1985!  A well documented story…in 1985, the first, and very popular, feline leukemia vaccine (aluminum adjuvanted) was licensed in the US. Being the first FeLV vaccine to reach the market, widespread use followed.  Also in 1985, sale of modified-live rabies vaccine in the US was withdrawn and replaced with killed, adjuvanted rabies vaccine.   Then, in1987, the State of Pennsylvania issued legislation that required, for the first time, all cats receive a rabies vaccine.  I was in 1991 that the Pathology Laboratory at the University of Pennsylvania, School of Veterinary Medicine reported a dramatic increase in the number of fibrosarcomas in cats.  They went on to note that these tumors were particularly aggressive, were occurring in younger, versus older, cats, and that the tumors occurred in a location where veterinarians commonly administer vaccine.  In 1991, the issue was raised that vaccines might, in fact, be the cause of fibrosarcoma formation in some cats. 

Third…it was 1993!  A study published in 1993 provided epidemiologic evidence to show causation between the administration of either FeLV and/or rabies vaccination and tumorigenesis in cats. 

Fourth…studies in the UK!  A 5-year study conducted in England in the mid-1990’s, funded by the government, evaluated adverse vaccine reactions in dogs and cats.  Reported results were quite striking in that the study showed cats receiving an adjuvanted FeLV vaccine (England is rabies-free, therefore rabies vaccine is rarely administered) had a 5 times greater occurrence of VAS than cats receiving only non-adjuvanted, modified live virus (MLV) vaccines. 

Other studies conducted in the US have demonstrated mutations in the tumor suppressor gene (tp53) in cats that developed fibrosarcoma following administration of adjuvanted vaccine. 

While these studies don’t prove a cause-and-effect relationship between the administration of adjuvanted vaccine and fibrosarcoma, the evidence is compelling!

In 2005, Merial introduced the first recombinant, FeLV vaccine…the only non-adjuvanted FeLV vaccine available in the US.  It is my opinion that this is an important step forward in the effort to reduce the risk of VAS in cats. The reason…

…today, veterinarians practicing in the US have more choices than ever before when it comes to selecting and administering feline vaccine.  Of particular importance is the fact that, with the exception of FIV vaccine, for every adjuvanted feline vaccine on the market, there is a non-adjuvanted vaccine licensed for use in cats. 

The reality is that we may never actually establish a definitive etiology behind VAS in cats…but, today, with the facts that do exist, there is good justification for avoiding the use of adjuvanted vaccine in cats as a means of mitigating the risk of VAS!

  Core and Non-Core Feline Vaccines 

Vaccine

Adjuvanted

Non-Adjuvanted

Panleukopenia (MLV)

 

X

Herpesvirus & Calicivirus (MLV)

 

X

Feline Leukemia

X

X

FIV

X only

 

Chlamydophila spp.

X

X

B. bronchiseptica (avirulent live)

 

X

Rabies

X

X

[1] NOTE:  Over the next 5-10 years recombinant (genetically engineered) vaccines are expected to become a prominent  technology used by manufacturers in the production of companion animal vaccines. Although measurable antibody titers may be associated with some of these products, others will NOT produce antibody that is measurable in vivo.  Instead, these vaccines induce a robust and sustained cell-mediated immune (CMI) response, especially important in viral (intracellular) infections.

 

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