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
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
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:
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.
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.
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.
Measuring Antibody response to natural infection in recovered
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.
Case Against Adjuvant
B. Ford, DVM, MS
ACVIM and (Hon) ACVPM
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:
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).
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.
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.
in the UK!
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)
studies conducted in the US have demonstrated mutations in the tumor
suppressor gene (tp53) in cats that developed fibrosarcoma following
administration of adjuvanted vaccine.
these studies don’t prove a
cause-and-effect relationship between the administration of adjuvanted
vaccine and fibrosarcoma, the evidence is compelling!
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…
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.
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!
and Non-Core Feline Vaccines
& Calicivirus (MLV)
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.