Measuring antibody titers is becoming common in practice—but remains confusing, even controversial.
When
and why has it become more common for veterinarians to measure antibody
titers when deciding whether to revaccinate cats and dogs
An
antibody titer is a measure of the concentration of antibodies in the
blood, as determined by a test involving repeatedly diluting a blood
sample and exposing those dilutions to an antigen. The shorthand is to
refer to all measurements of antibody concentration as titers
Dr.
Richard Ford, emeritus professor of internal medicine at the North
Carolina State University College of Veterinary Medicine, said factors
inside and outside the profession are driving the increase in antibody
titer testing.
In
the late 1990s and early 2000s, the American Association of Feline
Practitioners, AVMA, and American Animal Hospital Association released
guidelines on vaccination suggesting that core vaccines have a longer
duration of immunity than one year. The AAFP and AAHA guidelines
recommended vaccinating every three years. Dr. Ford said many practices
began measuring titers “to provide evidence to themselves that in fact
the vaccinations are lasting longer than one year.
”Part
of the impetus for the guidelines was concerns about the potential
adverse effects of vaccines. Recently, Dr. Ford said, concerns about
adverse effects of vaccines in children have spilled over into
veterinary medicine.
The
technology for measuring antibodies also has improved, he said. There
are now affordable point-of-care test kits that provide useful
information within 20 to 25 minutes. Dr. Ford said, “Two things loom,
and I think every veterinarian should be aware of this. One, what is the
indication for using the test? And, two, how do you interpret the test
results
”For
all forms of antibody testing, it remains confusing and even
controversial whether the results are a good measure of immunity.
According
to the AAHA guidelines, antibody testing is useful for monitoring
immunity to certain viruses in dogs. The AAFP guidelines recommend
defined revaccination intervals for cats. Guidelines from the World
Small Animal Veterinary Association favor antibody testing for
determining duration of immunity of core vaccines in dogs. But the
current AVMA “Vaccination Principles” sound a cautionary note.
Principles of titers
According
to the AVMA principles: “When serological titers are used to help
determine the vaccination/protection status of an animal, veterinarians
should make sure these data have been clinically correlated to
host-animal protection studies for the specific diseases and species
being tested. For most common vaccine antigens, the correlation between
serological response to vaccination, long-term serostatus, and
protection in the host animal has not been adequately established. The
lack of these data often precludes practitioner’s ability to make
well-informed vaccination decisions based on serostatus alone.
”Dr.
Laurel Gershwin, a professor who teaches immunology at the University
of California-Davis School of Veterinary Medicine, represents immunology
on the AVMA Council on Biologic and Therapeutic Agents, which has
oversight of the “Vaccination Principles.” The principles don’t make
recommendations on specific vaccines or specific vaccination intervals,
but Dr. Gershwin said there are good data that immunity from core
vaccines in cats and dogs should last for three years.
“For
those clients that are reticent about not having a distemper vaccine
every single year, for example, those are a great indication to go ahead
and do a titer,” she said. “Having said that, when we measure antibody,
antibody is only part of the equation
A
cat or dog could respond to a vaccine with a strong cell-mediated
immune response, which is difficult to measure outside a research
setting. She said, “Even if you have a titer that is less than what is
considered acceptable, that doesn’t necessarily mean that the pet would
get sick if he or she were challenged with just the street virus,
walking down the road and sniffing noses with a dog that was infected,
for example. But, obviously, one would want to boost those.
”Dr.
Gershwin said the gold standard in titer testing involves sending a
blood sample to a laboratory to, say, perform a virus neutralization
assay to measure antibodies to canine distemper virus or parvovirus or
to perform a hemagglutination inhibition test to measure antibodies to
parvovirus.
Titer
testing is a good idea for some cats and dogs, Dr. Gershwin believes.
These include animals that have a history of or genetic predisposition
to poor responsiveness to a vaccine, that have an allergic reaction to
or other adverse effect from a vaccine, or that have immunosuppression.
Titers in practice
The
AAHA Canine Vaccination Guidelines state that “despite the confusion
and controversy surrounding antibody testing,” the testing is useful for
monitoring immunity to canine distemper virus, canine parvovirus type
2, canine adenovirus type 1, and rabies virus. The guidelines note,
“Some clients are now having titers performed for CDV and CPV-2 in lieu
of revaccinating.
” I
get the impression that some veterinarians are just not doing any
vaccinations until the titer falls into the negative threshold level,
and then they boost. So that might mean some dogs or cats will go on for
multiple years without needing a vaccination. Some develop excellent
levels of antibody that are sustained virtually for their lives
following the initial vaccination series. And others don’t seem to
sustain them that well
.Dr. Richard Ford, emeritus professor of internal medicine, North Carolina State University College of Veterinary MedicineDr.
Ford of North Carolina State University, an author of the AAHA and AAFP
guidelines on vaccination, said point-of-care test kits that correspond
well to gold-standard titer testing are available for canine distemper
virus, canine parvovirus, and canine adenovirus as well as the
parvovirus that causes feline panleukopenia.
The
test kits have a variety of applications, he said. Animal shelters
could do titers during animal intake or during an outbreak to help
control disease without euthanasia. A veterinarian might finish the
vaccination series for a puppy, then test whether the dog has been
immunized before starting puppy socialization or doggy day care.
More
clients are asking whether booster vaccines are necessary, Dr. Ford
said, and the cost has come down for titer testing. He said, “I get the
impression that some veterinarians are just not doing any vaccinations
until the titer falls into the negative threshold level, and then they
boost. So that might mean some dogs or cats will go on for multiple
years without needing a vaccination. Some develop excellent levels of
antibody that are sustained virtually for their lives following the
initial vaccination series. And others don’t seem to sustain them that
well.
”Dr.
Ford uses the acronym PIE to help with interpretation of titer tests.
Depending on the nature of the disease, a positive result can imply
protection, infection, or exposure. A positive result on a titer test
for Lyme disease or leptospirosis implies infection. A positive result
on a titer test for ehrlichiosis implies exposure.
For
titer tests as with all tests, Dr. Ford added, practitioners should
consider data on the likelihood of false-positive and false-negative
results.AAFP recommendations
The
AAFP Feline Vaccination Advisory Panel Report states, “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.
”According
to the report, most cats that have a positive result on a titer test
for feline panleukopenia are immune to the disease. Titers for feline
herpesvirus-1 and feline calicivirus “may not necessarily correlate well
with protective immunity and should not be used to predict protection
in the future.” Titers for feline leukemia virus and feline
immunodeficiency virus “do not correlate with immunity and should not be
used to determine the need for vaccination.
”Shila
Nordone, who holds a doctorate in immunology and was an author on the
report, said, “We have yet to determine the role of cell-mediated
immunity in protection of the cat long term against specific diseases
post-immunization. Antibody titers do correlate with protection but are
by no means indicative of absolute protection.
”Vaccine
formulations vary quite a bit, Dr. Nordone said. The AAFP recommends
boostering when protection is likely to begin waning, about halfway
through the expected duration of immunity.
Dr.
Nordone said vaccines for feline panleukopenia are highly effective,
inducing sterilizing immunity, which means the virus is blocked from
replicating in the cat. She said, “FCV and FHV vaccines do not induce
sterilizing immunity but rather minimize clinical symptoms of disease.
Similarly, FIV and FeLV vaccines don’t induce sterilizing immunity
against the pathogens.
”She
concluded, “My bias, as an immunologist, is to avoid overimmunization
and follow recommendations in order to maintain full protection.
”Favoring titers
The
Canine Vaccination Guidelines within the WSAVA Guidelines for the
Vaccination of Dogs and Cats state that, while antibody testing still
can be relatively expensive, “The principles of ‘evidence-based
veterinary medicine’ suggest that testing for antibody status (for
either puppies or adult dogs) should be better practice than simply
administering a vaccine booster on the basis that this would be ‘safe
and cost less.’
”Some
dogs maintain antibodies for their entire lives to canine distemper,
canine parvovirus, and canine adenovirus, said Dr. Ronald D. Schultz,
professor of immunology and founding chair of the Department of
Pathobiological Sciences at the University of Wisconsin-Madison School
of Veterinary Medicine and an author of the WSAVA and AAHA guidelines.
In
his controlled studies, he has found that dogs maintain immunity to
CDV, CPV-2, and CAV seven to nine years after vaccination, as proved by
protection against virulent challenge. He said, “The presence of active
antibody response to these viruses is a clear indication of protection.
There is no confusion on this point.
”Dr.
Schultz noted that the canine distemper, canine and feline parvovirus,
and canine adenovirus core vaccines are all modified-live virus
vaccines. In general, he said, modified-live virus vaccines provide
longer-term immunity than killed virus vaccines do.
“We
can use titers to know whether or not the animal does need to be
revaccinated, or we can simply go on a schedule and just revaccinate,”
he said. While few practitioners would have thought of doing titers 10
years ago, he sees more and more titer testing today. He said, “Dr.
Laurie Larson in my laboratory is running thousands of gold-standard
titer tests per year, and the push is coming from owners who wish to
avoid unnecessary booster vaccination.
”Dr.
Schultz emphasized, “This is something that the owners just need to
recognize: how important those core vaccines are. Every puppy and every
kitten should receive them. Antibody testing assures us that the dog or
cat is actually protected by the vaccine, or not, and is a very useful
tool for every small animal practitioner. This is the only practical
method to be certain the animal has developed an immune response to a
given core vaccine.
”Dr.
Gershwin of the AVMA Council on Biologic and Therapeutic Agents
concluded, “Pet owners need to work with their veterinarians to
determine the best schedule of immunizations for their pet. This will be
dependent upon individual situations, such as allergic reactivity and
factors such as being on an immunosuppressive drug.
What exactly is an antibody titer?
In
brief: An antibody titer is a measurement of the concentration of
antibodies in the blood, as determined by a test involving repeatedly
diluting a blood sample and exposing those dilutions to an antigen.
Dr.
Laurel Gershwin, who teaches immunology at the University of
California-Davis, added: “The last dilution of the patient’s serum that
produces the positive endpoint—this will differ depending upon the type
of assay—is used to determine the titer. Hence, the more you can dilute
the serum and get the appropriate endpoint reaction, the more antibody
there is.”