University and Hayward Foundation Study on Vaccines
15 years, some Great Dane breeders have postulated the adverse effects of the
aggressive use of vaccines on the immature (puppy) immune system. This
concern led these breeders to a more conservative approach to vaccinations,
the monitoring of antibody titers before boosters were given, or in some cases
safe alternatives to conventional practice were invoked.
the last two years a cutting edge scientific research study has been conducted
at Purdue University, under the direction of Larry Glickman, VDM,PhD and his
associate Dr. Harm HogenEsch (Curricula Vitae and the impressive credentials
of these scientists are included for your review). The study proposal is to
investigate the autoimmune responses to vaccines in dogs. This study, at
Purdue, was conceptualized by Great Dane people, and subsequently funded (±
$175,000.00) by a Great Dane friendly organization called the John &
Winifred Hayward Foundation. Originally, it was considered ideal to conduct
the study with a colony of Great Danes. However, the feasibility and
practicality of maintaining and housing a controlled group of Great Danes was
economically out of reach. Therefore, the study identified the Beagle as
the canine of choice, but recognized the applications of any results to the
canine population as a whole, including Great Danes.
study has produced some dramatic results, with concrete and clear evidence
that there are adverse events elicited as a result of the use of vaccines
following manufacturer's recommendations. (Review the following article for a
more complete picture of study results.)
Dr. LaRosa's (Trustee of the Hayward Foundation) article (following), he
states that a number of autoantibodies to several critical proteins and DNA
were identified in the vaccinated group. Identifying these autoimmune
antibodies, and monitoring their titers may lead, in addition to the
thyroiditis conditions, a better understanding of the role of vaccines in
soliciting adverse events that contribute to problematic conditions observed
in the Great Dane, such as Cardiomyopathy, and Various Bone related disorders.
positive outcomes of the study at Purdue will hopefully be the identification
of a number of genetic markers that will facilitate a brighter and healthier
future for our breed, as well as recommendations for safer vaccines and their
Hayward Foundation is limited by its charter to investigate Human Genetic
Disorders, therefore its ability to significantly fund this study further
falls outside of the realm of its charter. However, the Trustees of the
Hayward Foundation have committed an additional $25,000.00 to help in the
maintenance of this colony until further funding is identified.
has stated that the colony will be lost unless further and immediate funding
is identified to maintain the colony . Dr. Glickman is applying to the
AKC Foundation and the NIH (National Institute of Health) for funding. Two
years of research will not be lost but the future of this work which relies on
maintaining the colony for some time to come will be lost.
Possible Etiology of Autoimmune Diseases
: William R. La Rosa, M.D. (Trustee)
Hayward Foundation is dedicated to research and eradication of human genetic
diseases. There is much anecdotal hearsay about the safety of vaccines
in dogs as well as in humans. The Vaccine Safety Committee recently
emphasized the need for more definitive research on possible adverse effects
during the development of new vaccines and vaccine combinations. (National
Academy Press, Washington D.C. 1994).
a dog vaccine safety issue was brought to our attention by Laura Kiaulenas, a
prominent Harlequin Great Dane breeder, and after reading articles by Jean
Dodds DVM, we decided to fund a study to prove or disprove the supposition of
multiple diseases, acute and chronic, caused by vaccination. If indeed,
many breeders are correct, then is the dog a canary sentinel, and are human
similarly being affected, and if so can we identify the dog or human who is
genetically susceptible to these reactions ?
were fortunate that prominent and respected researchers, Drs. Larry T.
Glickman, Harm HogenEsch, Juan I. Azona-Olivera, J. Catherine Scott-Montcrieff,
and Paul W. Snyder of Purdue University, School of Veterinary Medicine, agreed
to undertake the study. The results are enlightening and they are
enthusiastically working on the second phase, a study of longer duration.
presented a paper to the International Veterinary Vaccines and Diagnostics
Conference, July 27 - 31, 1997, in Madison, Wisconsin, hosted by the
University of Wisconsin. These proceedings have been published in
Advances in Veterinary Science and Comparative Medicine . Another manuscript:
Vaccine Induced Serum Autoantibodies in Young Beagles , has been submitted to
a human immunology journal Clinical Immunology and Immmunopathology.
study was based on the increasing concern among veterinarians and breeders
that current vaccination protocols adversely affect the health of dogs.
This concern has largely been based on anecdotal and circumstantial evidence.
They studied the effects of routinely used vaccination protocol on the immune
and endocrine systems of Beagles.
control group was not vaccinated and the other group was vaccinated with a
commercial multivalent vaccine at 8, 10, 12, 16, and 20 weeks of age and with
a rabies vaccine at 16 weeks of age.
definition of autoimmune disease is now necessary. In dogs as well as
humans, the body sometimes forms antibodies against itself (self antigens)
which can lead to diseases of the pancreas (diabetes), thyroid (Hashimoto's
Disease), collagen and fibronectin (Scleroderma, Lupus),cardiolipin (Cardiomyopathy),
etc. The body literally attacks itself to cause the autoimmune disease.
vaccinated group developed significant levels of autoantibodies against:
fibronectin, laminin, DNA, albumin, Cytochrome C, transferrin, cardiolipin,
collagen. The responses varied among individual animals, probably reflecting
genetic differences. The clinical significance of those autoantibodies
remains to be determined, but speculation must be that something in the
vaccines is one of the etiologies (in the genetically susceptible dog) of such
diseases as Cardiomyopathy, Lupus Erythematosus, Glomerulonephritis, etc.
I apologise for using these technical terms but this is a complex study and
adds validity to the report.
diseases are quite common in dogs as well as in humans, but much easier to
study in dogs, especially since various breeds have genetic susceptibility or
predisposition. The high prevalence of autoimmune disease in specific
breeds makes it easier to search for the genetic markers. Humans are
much more diverse and therefore more difficult to study.
hope that many Breed Associations and the AKC Foundation will join us in
expanding these studies with the needed research funds. Longer term
studies are needed to determine the clinical importance of vaccine-induced
autoantibodies and to identify markers of genetic susceptibility.
are truly remarkable results. The next step is to study the development
of safer vaccines, or possibly modify the recommended dosages, and the timing
of vaccinations. Many vaccines, including a vaccine for use in humans,
contain fibronectin. This appears to be a common contaminant.
Other antigens will be studied.
general theme of the Conference was that vaccine immunity lasts longer than
the manufacturer claims; rabies is probably effective for at least 3 years and
we are probably over-vaccinating our dogs. Even the vaccine industry
tells you that there is never 100% protection. Therefore disease is seen
even in vaccinated groups. In Europe, vaccines are prohibited once the
disease is eliminated because the fear of reversion to virulence of the
modified live virus.
diseases in dogs are clinically similar to those in humans. We hope that
Veterinary and Medical Schools will continue and expand these preliminary
research studies. Our companion dogs are crashing all around us and
maybe we are now finding one of the sources of the problems. It has been
so easy to point fingers at breeders but they may not be entirely at fault.
Let us continue this important research to help our future generations of dogs
and possibly children. Yes, indiscriminate breeding can genetically
predispose the dog but is the trigger mechanism indiscriminate vaccinations
personal interpretation of the above information in brief is: (from Dr. La
These studies appear to support the conclusions of some breeders that multiple
vaccinations may be harmful to dogs. Be cautious and keep current in the
Current vaccines induce autoantibodies. Contaminants may be part of the
We need to research and explain the mechanism. Does it alter the DNA
causing genetic abnormality or is the susceptible gene already in place? Can
we find the genetic marker to avoid the adverse reaction of vaccination ?
The dog is a good model for study because different breeds already have
susceptibility to specific diseases and genetic markers will be easier to find
than in other diverse animals (and humans).
What is the solution or cure, and especially how is this applicable to humans.
Most current vaccines are effective in preventing disease, but they may be
administered more frequently than is actually required.
study certainly points out the preliminary conclusions that have also been
done with the Canine Health Concern in the UK.
Of Vaccination On The Endocrine And Immune Systems of Dogs
University, November 1, 1999
Harm HogenEsch and Larry T. Glickman
has been growing among owners, breeders, and veterinarians that current
vaccines cause immune-mediated diseases in dogs. Vaccination is highly
effective in preventing infectious disease, but the safety of many vaccines
and the frequency of their administration are being questioned. The
Vaccine Research Group at the Purdue University School of Veterinary Medicine
has been conducting several studies to address these issues. In one such
study, we are trying to determine if current vaccines cause changes in the
immune system of the dog that will eventually result in life-threatening
immune mediated diseases.
Beagles being used in this study were bred by us and then vaccinated following
a typical schedule used for pet dogs. These Beagles have been closely
followed for three years with blood and other tests performed at regular
date, routing vaccination of these Beagles has not caused any overt signs of
clinical disease. However, the blood of all the vaccinated dogs contains
significantly elevated concentrations of antibodies directed against proteins
that are present in commercial vaccines as contaminants of the production
process. None of the unvaccinated control dogs has had a similar
increase in these antibodies. These proteins are typically of bovine
origin since fetal calf serum is used to grow the viruses for vaccine
production. The close similarity in structure of the bovine proteins to
dog proteins results in a situation whereby the antibodies produced by the
vaccinated dogs may cross-react with dog tissue proteins in a process similar
in other animal species suggest that these autoantibodies might eventually
cause diseases in the vaccinated animals, but these Beagle dogs will need to
be followed longer to determine if this is the case. In addition, the
pattern of individual responses of the immunesystem to vaccination in this
study suggests a possible genetic predisposition to autoimmunity.
study described above is unique in that it attempts to determine if
vaccinations that dogs routinely receive throughout their life have a
cumulative adverse effect. The only way this is possible is under
experimental conditions where one group of dogs remains unvaccinated.
vaccine studies we are conducting both in Beagles and in pet dogs under
natural conditions are designed to answer the question: "Does vaccination
play a role in autoimmunity, how safe are currently used vaccines, and how
often should these vaccines be administered?"
March, 2000 I personally contacted Dr. Glickman regarding this study and in
the course of events that followed; Dr. Glickman has agreed to extend the
study to our breed, the Great Dane. In the initial conversations, Dr. Glickman
postulated that to continue the study further would cost in the neighborhood
of one to two million dollars. When I told him that we have a number of Great
Danes that are totally unvaccinated and could act as 'controls'. he came back
very excited and proposed the further study with Great Danes.
Study will be divided into 3 groups: Unvaccinated..; Vaccinated without annual
boosters and Vaccinated with annual vaccines
Report to the Hayward Foundation and
Great Dane Health Foundation of a Study Titled
in Great Danes
of Veterinary Pathobiology
of Veterinary Clinical Sciences
University School of Veterinary Medicine
Lafayette, IN 47907-1243
is great concern among dog owners and veterinarians that some currently used
vaccines or vaccine practices (e.g., yearly vaccination) adversely affect the
health of dogs. Although few question the effectiveness of current
vaccines for preventing common infectious diseases such as parvovirus,
distemper, and rabies, the potential adverse effects of these vaccines are
just becoming apparent. More and more owners are asking whether some
vaccines used today could be responsible for the increasing prevalence of
autoimmune diseases such as hypothyroidism, Addison's (hypoadrenocorticism),
and hemolytic anemia, especially when the vaccines are administered annually.
The situation has become so troublesome for some dog owners; they have stopped
vaccinating their dogs entirely. The risk versus benefits of vaccinating
however cannot be fully evaluated without a clearer understanding of the
frequency and types of adverse events that result from vaccination. The
term vaccinosis describes the abnormal physiologic changes or clinical
diseases associated either directly or indirectly, with the administration of
a vaccine. Such adverse events may be obvious when they occur soon after
vaccination, but are more difficult to identify when their onset is delayed by
months or even years following vaccination. Yet, there has been little
research conducted on the frequency or severity of vaccine-related adverse
reactions in dogs.
compare the health of fully vaccinated, partially vaccinated, and
unvaccinated, Great Dane dogs with respect to their immune status and to
identify specific vaccine types associated with a higher concentration of
auto-antibodies. Of particular interest was the concentration of
antibodies produced against the dogs’ own thyroid gland, since an increased
level of thyroid auto-antibodies has been associated with a greater
probability of developing thyroid disease. For example, in one study,
approximately 20% of anti-thyroglobulin positive dogs without overt signs of
hypothyroidism developed thyroid dysfunction within 1-year.
compared with unvaccinated Great Dane dogs have:
A significantly higher serum concentration of antibodies directed against
their own tissues
A significantly higher serum concentration of TSH and lower concentrations of
T3 and T4 hormones
A significantly higher proportion of dogs with a history or clinical signs of
an autoimmune disease, particularly hypothyroidism
Danes for the proposed study were recruited through personal contacts, the
Purdue University School of Veterinary Medicine website and the website of the
Great Dane Health Foundation of America. The intent was to enroll 100 dogs
divided among the following groups: 1) Dogs with no history of vaccination
(never vaccinated), 2) Dogs with a history of vaccination only in the first
year of life (partially vaccinated), and 3) Dogs that were vaccinated
regularly throughout their life (fully vaccinated). The dogs were
required to be 2 years of age or older and of either sex or neuter status to
enter the study. Each owner was asked to complete a 15-page
questionnaire that was developed specifically for this study. It
included questions about their dog's age, weight, sex and neuter status, coat
color, vaccine history, previous illnesses, diet and nutritional supplements
used, medications, flea and tick control, housing, environment, etc.
Each owner was also asked to take his or her dog(s) to a veterinarian to
collect 10ml of blood, centrifuge the blood specimen, and send the serum on
ice by express mail to the laboratory of Dr. Harm HogenEsch at Purdue
University in W. Lafayette, IN. The veterinarian was also asked to
conduct a physical examination and record any current conditions or diseases
on a form provided to them by Purdue.
serum specimens were assayed for the following:
Total immunoglobulins IgA, IgG, and IgM
Antibodies against bovine fibronectin, bovine thyroglobulin, canine
thyroglobulin, bovine DNA, murine laminin, and porcine insulin
Acute phase protein serum amyloid
including TSH, T3, and T4
Antibodies against canine distemper, parvovirus, and rabies, in order to
validate the vaccination status of the dog
test results and owner reported information were compared between the three
groups using Analysis of Variance and Covariance, T-tests, and Chi-square
tests. A p-value of <0.05 was considered to be statistically
significant. All of the information collected from owners and
veterinarians are being kept strictly confidential.
total of 75 Great Danes who met the eligibility requirements were enrolled in
the study. A majority of these 75 dogs were female (47 dogs), neutered (41
dogs), and in average or optimum body condition (59 dogs). The mean
(standard deviation) age was 5.7 (2.3) years with a minimum of 2.2 years and a
maximum of 10.5 years; the median age was 5.0 years. Only 15 of the dogs
had never been vaccinated during their life Eighteen dogs had never received a
distemper vaccine, 19 dogs had never received a parvovirus vaccine, and 23 had
never been vaccinated against rabies. It should be noted that totally
unvaccinated dogs were much harder to recruit into the study than vaccinated
dogs, because many owners of unvaccinated dogs did not have a regular
veterinarian. Therefore, they either could not or would not provide us
with a serum sample or a questionnaire completed by a veterinarian. Very
few dogs, whether vaccinated or not, had a history of either an endocrine or
autoimmune disorder. The disease most commonly reported by owners (7 dogs) or
their veterinarians (6 dogs) was hypothyroidism.
dogs in this study were divided into three vaccine groups (never vaccinated,
partially vaccinated, and fully vaccinated) based on owner reports.
Therefore, it was important to document the validity of these reports.
This was done by measuring the antibody titer against distemper, parvovirus,
and rabies, and comparing them with the owners’ answer to the question
“How frequently and when was your dog vaccinated against distemper,
parvovirus, and rabies?” A very significant and strong correlation was
found between the owners’ responses regarding the pattern of administration
of distemper vaccine and the distemper antibody titer. A similarly strong
relationship was found for rabies. However, there was no clear-cut
relationship between the parvovirus vaccine history and antibody titers to
parvovirus. In fact, the parvovirus antibody titers of dogs belonging to
owners who said they never vaccinated or only sporadically vaccinated their
dog for parvovirus were not significantly different from dogs belonging to
owners who claimed they had never vaccinated their dog against parvovirus. The
findings with regard to rabies and distemper antibody titers support the
validity of the owners’ answers on the questionnaire. It is not
surprising however, that many dogs unvaccinated for parvovirus based on
owners’ reports had antibody titers as high or higher against parvovirus
than dogs that were reported to have been vaccinated against parvovirus either
regularly or sporadically. Parvovirus is commonly shed in dog
(either the vaccine or natural strain) and contaminates the environment of
parks, homes, kennels, etc. Once in the environment it is highly
resistant to a wide range of climatic conditions and is readily transmitted
from dog to dog, by fecal oral contact. In contrast, distemper and
rabies virus are not stable in the environment and transmission from dog to
dog requires closer contact between individuals. Therefore, we believe
the vaccine groups (never vaccinated, partially vaccinated, and fully
vaccinated) to which dogs were assigned in this study were valid.
dogs vaccinated at least once in their lifetime did not differ significantly
from those that were never vaccinated with respect to their gender, body
condition, age, weight, and height. However, the unvaccinated dogs were
significantly less likely to have been neutered. Also, there were
significant differences between the vaccine groups related to whether the dog
had a regular veterinarian and if it had received routine medication for
heartworm or flea/tick prevention. In general, dogs in the never vaccinated
group were less likely to have received routine preventive medical care or had
been surgically neutered, compared with dogs in the vaccinated group.
However, dogs reported by owners as never being vaccinated were not more
likely to have a history of non-infectious conditions including cancer,
allergies, endocrine abnormalities, autoimmunity, urinary tract problems,
neurological disease, musculoskeletal disease, or genetic problems.
were 7 adverse reactions reported by Great Dane owners. Three reactions
were to vaccinations while four were to drugs or anesthesia. None of
these adverse reactions had deleterious long-term consequences.
compared with unvaccinated Great Dane dogs have a significantly higher serum
concentration of antibodies directed against their own tissues, particularly
the thyroid gland
or inflammation of the thyroid gland is thought to be a precursor of clinical
hypothyroidism in dogs. Approximately 40% of dogs with thyroiditis have
an increased concentration of antibodies in their blood directed against
thyroid tissue. It is not known what triggers production of these
thyroid autoantibodies. Environmental factors such as estrogenic-like
chemicals that disrupt hormone function and viruses have been suggested as
causing the dog’s immune system to produce antibodies that destroy its own
tissues. Recently, evidence from experiments in Beagles and
epidemiological studies of owned dogs indicate that commonly used vaccines may
act to trigger autoimmune responses, particularly against the thyroid gland.
For this reason we evaluated whether dogs receiving regular vaccinations for
distemper, parvovirus, and rabies, had higher levels of auto-antibodies in
their blood than dogs never vaccinated or partially vaccinated.
Furthermore, we looked for a positive relationship between the number of
vaccines a dog had received and the auto-antibody titer. While our
primary interest was in auto-antibodies directed against the thyroid gland, we
also measured those directed against connective tissue components (fibronectin),
laminin, DNA, and insulin, since such antibodies have been associated with
health disorders in people and dogs.
in previous studies, the strongest positive relationship was shown between
previous vaccination for rabies and an antibody response to bovine fibronectin
and bovine thyroglobulin. A strong positive association was also
observed between vaccination for distemper or parvovirus and bovine
thyroglobulin. In contrast, there was only a weak positive relationship
between previous vaccination for parvovirus and antibody to canine
thyroglobulin. It thus appears that vaccinated dogs in this study were
producing antibodies that reacted to bovine contaminants plus adjuvant in the
canine vaccines. This reaction was evidenced by higher concentrations of
antibodies against bovine thyroglobulin, but these antibodies only weakly
cross-reacted with canine thyroglobulin. Similarly, the increasing
antibody titers to bovine laminin in dogs with regular rabies vaccination, was
likely caused by contaminants in the rabies vaccine combined with the presence
of adjuvant. These findings alone do not tell us whether the serum
auto-antibodies might be responsible for clinical autoimmunity in dogs. They
do however warrant further investigation o determine if they play a causal
role in thyroid disease.
concentration of anti-bovine thyroglobulin antibodies in the serum was
significantly correlated with the concentration of anti-canine thyroglobulin
antibodies Each unit increase in anti-bovine thyroglobulin antibodies
was associated with a 0.07 increase in anti-canine thyroglobulin antibodies.
This relationship is not surprising, since we previously hypothesized that
dogs respond to impurities of bovine origin in canine vaccines by producing
anti-bovine thyroglobulin antibodies that then cross-react with canine-thyroglobulin.
contrast to the findings for specific auto-antibodies, no relationship was
found between the vaccine history of dogs and the concentration of
immunoglobulins IgG, IgM, IgA, or serum level of amyloid protein (SAA).
compared with unvaccinated Great Dane dogs have a significantly higher serum
concentration of TSH and lower concentrations of T3 and T4 hormones
diagnosed with clinical hypothyroidism typically have lower serum
concentrations of T3 and/or T4 hormones and an increased concentration of
serum TSH hormone. The serum T3 and serum T4 concentrations were
consistently lower for Great Danes in this study that were previously
vaccinated compared with those never vaccinated, but these differences were
not statistically significant. However, the vaccinated dogs in this
study also had consistently lower serum concentrations of TSH compared with
dogs that were never vaccinated. In addition, no significant correlation was
found between the concentration of TSH in serum and either the T3 or T4
concentration. These findings when taken together, suggest the
differences observed in thyroid hormone levels between dogs in the three
vaccine groups, were more likely associated with non-thyroidal causes rather
than any abnormality in their thyroid function. It is also possible that
vaccination results in substances in blood that interfere with the laboratory
assay for T3, T4, and TSH. These findings warrant additional studies.
compared with unvaccinated Great Dane dogs have a significantly higher risk of
autoimmune diseases, particularly hypothyroidism
were unable to test this hypothesis because only one owner of a dog in the
unvaccinated group reported having a regular veterinarian or even using a
veterinarian when their dog was ill. Since the diagnosis of an
autoimmune disease requires specific tests that must be requested and or
preformed by a veterinary laboratory, it was impossible to know if dogs in the
unvaccinated group ever experienced an autoimmune disease. We did not
anticipate this when the study was designed. We assumed that all Great
Dane owners interested in participating in this health-related study would
either use veterinary services regularly or would take their dog to a
veterinarian when it was sick. Because many of the owners of dogs in
the never vaccinated group had not established a veterinary-client
relationship, it was difficult to even obtain blood samples for these dogs.
in two previous studies we conducted, we confirmed that vaccinated dogs when
compared with non-vaccinated dogs have a higher concentration of antibodies in
their serum directed against bovine proteins such as thyroglobulin and
fibronectin. These antibodies are probably produced in response to
contaminants from fetal calf serum commonly used to make canine vaccines.
These anti-bovine antibodies probably then cross-react with a dog’s own
thyroglobulin and fibronectin, resulting in detectable concentrations of
autoantibodies in their serum. It would be difficult to design a study
in pet dogs to prove this process of cross-reaction between bovine and canine
proteins actually causes clinical signs of autoimmune disease in vaccinated
dogs. There were too many differences between the vaccinated and
unvaccinated Great Danes in the present study to further explore the clinical
consequences of vaccine-related auto-antibodies produced against fibronectin
best way to determine if repeated vaccination of Great Danes causes autoimmune
disease would be to prospectively follow a large number of regularly
vaccinated and non-vaccinated dogs from birth, performing annual physical
examinations and blood tests for autoimmunity. In our experience
however, it is unlikely owners of unvaccinated Great Danes would actively
participate in such a study. Therefore, the long-term potential adverse
consequence of repeated vaccination is likely to remain unknown. Until
further studies are done, we recommend that all Great Danes continue to be
vaccinated using core vaccines as per guidelines published by the American
Animal Hospital Association. You should discuss these guidelines with
your veterinarian and work together to determine how they can be
individualized to fit your dog’s life style.
would like to thank all of the Great Dane owners for both their participation
and interest in this study. We enjoyed communicating with many of you
over the past few years and appreciate your efforts. We plan to continue
our research to make current canine vaccines safer for all dog breeds.
We also thank the Great Dane Health Foundation and the Hayward Genetic
Foundation for their sponsorship of this study and for their support of canine
health research at the Purdue University School of Veterinary Medicine.
more in-depth summary of this study is posted at: www.vet.purdue.edu/epi/gdhstudy.htm