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Protocols for Dogs Predisposed to Vaccine Reactions 

W. Jean Dodds, DVM 

Journal of the American Animal Hospital Association 

May 1, 2001 

Vaccination

W. Jean Dodds, DVM Keywords: Canine; Vaccination Protocols for Dogs; Vaccine

Reactions 

GUEST Editorial 

There is increasing evidence in veterinary medicine that vaccines can

trigger immune mediated and other chronic disorders (i. e., vaccinosis),

especially in certain apparently predisposed breeds. 16 Accordingly,

clinicians need to be aware of this potential and offer alternative

approaches for preventing infectious diseases in these animals. Such

alternatives to current vaccine practices include: measuring serum antibody

titers; avoidance of unnecessary vaccines or over vaccinating; and using

caution in vaccinating ill, geriatric, debilitated, or febrile individuals,

and animals from breeds or families known to be at increased risk for

immunological reactions. 3,58 Fortunately, the most common effect of vaccine

administration is the stimulation of an immune response that conveys

protection for that disease. This outcome has resulted in the widespread

reduction in morbidity and mortality from the many infectious diseases that

have plagued both animals and humans. An excellent example of this benefit

is the global eradication of smallpox as the result of a comprehensive

immunization program. Despite these intended benefits, however, vaccination

does carry with it attendant risks.

Adverse Effects of Vaccines 

As the most commonly recognized adverse effect of vaccination is an

immediate hypersensitivity or anaphylactic reaction, practitioners are less

familiar with the more rare but equally serious acute or chronic immune

mediated syndromes that can occur. The veterinary profession and vaccine

industry have traditionally emphasized the importance of giving a series of

vaccinations to young animals to prevent infectious diseases, to the extent

that this practice is considered routine and is generally safe for the

majority of animals. Few clinicians are prepared, therefore, for

encountering an adverse event and may overlook or even deny the possibility.

Beyond the immediate hypersensitivity reactions, other acute events tend to

occur 24 to 72 hours afterward, or 7 to 45 days later in a delayed type

immunological response. 1,6,9,10 Even more delayed adverse effects include

mortality from hightitered measles vaccine in infants, canine distemper

antibodies in joint diseases of dogs, and feline injection site 

fibrosarcomas. 3,11 The increasing antigenic load presented to the host

individual by modified live virus (MLV) vaccines is presumed to be

responsible for the immunological challenge that can result in a delayed

hypersensitivity reaction. 6,9 The clinical signs associated with

nonanaphylactic vaccine reactions typically include fever, stiffness, sore

joints and abdominal tenderness, susceptibility to infections, neurological

disorders and encephalitis, autoimmune hemolytic anemia (AIHA) resulting in

icterus, or immune mediated thrombocytopenia (ITP) resulting in petechiae

and ecchymotic hemorrhage. 14,9,10,1215 Hepatic enzymes may be markedly

elevated, and liver or kidney failure may occur by itself or accompany bone

marrow suppression. 3 Furthermore, MLV vaccination has been associated with

the development of transient seizures in puppies and adult dogs of breeds or

crossbreeds susceptible to immune mediated diseases, especially those

involving hematological or endocrine tissues (e. g., AIHA, ITP, autoimmune

thyroiditis). 13 Postvaccinal polyneuropathy is a recognized entity

associated occasionally with the use of distemper, parvovirus, rabies, and

possibly other vaccines. 3,6,9 This can result in various clinical signs,

including muscular atrophy, inhibition or interruption of neuronal control

of tissue and organ function, incoordination, and weakness. 3 Therefore, we

have the responsibility to advise companion animal breeders and caregivers

of the potential for genetically susceptible littermates and relatives that

are at increased risk for similar adverse vaccine reactions. 15 Commercial

vaccines, on rare occasion, can also be contaminated with other adventitious

viral agents, 6,16 which can produce significant untoward effects such as

occurred when a commercial canine parvovirus vaccine was contaminated by

blue tongue virus. It produced abortion and death when given to pregnant

dogs 16 and was linked causally to the ill advised but all too common

practice of vaccinating pregnant animals. 

The potential for side effects such as promotion of chronic disease states

in male and non pregnant female dogs receiving this lot of vaccine remains

in question, although there have been anecdotal reports of reduced stamina

and renal dysfunction in performance sled dogs. 3 Recently, a vaccine

manufacturer had to recall all biological products containing a distemper

component, because they were associated with a higher than expected rate of

central nervous system postvaccinal reactions 1 to 2 weeks following

administration. 3 

If, as a profession, we conclude that we are over vaccinating, other issues

come to bare, such as the needless client dollars spent on vaccines, despite

the well intentioned solicitation of clients to encourage annual booster

vaccinations so that pets also can receive a wellness examination. 5 Giving

annual boosters when they are not necessary has the client paying for a

service which is likely to be of little benefit to the pet‚s existing level

of protection against these infectious diseases. It also increases the risk

of adverse reactions from the repeated exposure to foreign substances. 

Polyvalent MLV vaccines, which multiply in the host, elicit a stronger

antigenic challenge to the animal and should mount a more effective and

sustained immune response. 5,6,9 However, this can overwhelm the immune

compromised or even healthy host that has ongoing exposure to other

environmental stimuli as well as a genetic predisposition that promotes

adverse response to viral challenge. 13,9,13 The recently weaned young puppy

or kitten being placed in a new environment may be at particular risk.

Furthermore, while the frequency of vaccinations is usually spaced 2 to 3

weeks apart, some veterinarians have advocated vaccination once a week in

stressful situations. This practice makes little sense, scientifically or

medically. 5 An augmented immune response to vaccination is seen in dogs

with preexisting inhalant allergies (i. e., atopy) to pollens. 3

Furthermore, the increasing current problems with allergic and immunological

diseases have been linked to the introduction of MLV vaccines more than 20

years ago. 6 While other environmental factors no doubt have a contributing

role, the introduction of these vaccine antigens and their environmental

shedding may provide the final insult that exceeds the immunological

tolerance threshold of some individuals in the pet population. 

Predisposed Breeds 

Twenty years ago, this author began studying families of dogs with an

apparent increased frequency of immune mediated hematological disease (i.

e., AIHA, ITP, or both). 1,2 

Among the more commonly recognized predisposed breeds were the Akita,

American cocker spaniel, German shepherd dog, golden retriever, Irish

setter, Great Dane, Kerry blue terrier, and all dachshund and poodle

varieties; but predisposition was found especially in the standard poodle,

longhaired dachshund, Old English sheepdog, Scottish terrier, Shetland

sheepdog, shih tzu, vizsla, and Weimaraner, as well as breeds of white or

predominantly white coat color or with coat color dilution 

 blue and

fawn Doberman pinschers, the merle collie, Australian shepherd, Shetland

sheepdog, and harlequin Great Dane). 13 Recently, other investigators have

noted the relatively high frequency of AIHA, ITP, or both in American cocker

spaniels 10 and Old English sheepdogs. 13 A significant proportion of these

animals had been vaccinated with monovalent or polyvalent vaccines within

the 30 to 45day period prior to the onset of their autoimmune disease.

1,2,10 Furthermore, the same breeds listed above appear to be more

susceptible to other adverse vaccine reactions, particularly postvaccinal

seizures, high fevers, and painful episodes of hypertrophic osteodystrophy

(HOD). 3 For animals that have experienced an adverse vaccine reaction, the

recommendation is often to refrain from vaccinating these animals until at

least after puberty, and instead to measure serological antibody titers

against the various diseases for which vaccination has been given. This

recommendation raises an issue with the legal requirement for rabies

vaccination. 

As rabies vaccines are strongly immunogenic and are known to elicit adverse

neurological reactions, 3,5 it would be advisable to postpone rabies

vaccination for such cases. A letter from the primary care veterinarian

stating the reason for requesting a waiver of rabies vaccination for puppies

or adults with documented serious adverse vaccine reactions should suffice. 

As further examples, findings from the author‚s large, accumulated database

of three susceptible breeds are summarized below. 

Vaccine Associated Disease in Old English Sheepdogs 

Old English sheepdogs appear to be predisposed to a variety of autoimmune

diseases. 13,13 Of these, the most commonly seen are AIHA, ITP, thyroiditis,

and Addison‚s disease. 2,17 

Between 1980 and 1990, this author studied 162 cases of immune mediated

hematological diseases in this breed. One hundred twenty nine of these cases

had AIHA, ITP, or both as a feature of their disease. Vaccination within the

previous 30 days was the only identified triggering event in seven cases and

was an apparent contributing factor in another 115 cases. 2 Thyroid disease

was recognized as either a primary or secondary problem in 71 cases, which

is likely an underestimate of the true incidence, as thyroid function tests

were not run or were inconclusive in most of the other cases. 

Experience with a particular Old English sheepdog family supported a genetic

predisposition to autoimmune thyroiditis, Addison‚s disease, and AIHA or ITP

or bothÌ an example of the polyglandular autoimmune syndrome. 2,17 Pedigrees

were available from 108 of the 162 Old English sheepdog cases of autoimmune

disease; a close relationship was found among all but seven of the affected

dogs. 2 Two of three pedigrees available from the studies of Day and Penhale

13 were also related to this large North American study group. 

Vaccine Associated Disease in Young Akitas 

Akitas also are subject to a variety of immune mediated disorders, including

VogtKoyanagiHarada syndrome (VKH), pemphigus, and heritable juvenile onset

immune mediated polyarthritis (IMPA). 3,14 Juvenile onset IMPA occurs in

Akitas less than 8 months of age. Of 11 closely related puppies in the

author‚s case series, the mean age of onset was 14 weeks. 3 Initial signs

appeared 3 to 29 days following vaccination with polyvalent MLV or killed

virus or both, with a mean reaction time of 14 days. All had profound joint

pain and cyclic febrile illness lasting 24 to 48 hours. Hemograms revealed

mild non regenerative anemia, neutrophilic leukocytosis, and occasional

thrombocytopenia. Joint aspiration and radiography indicated non septic, non

erosive arthritis. Despite treatment for immune mediated disease and

pyrexia, all eight dogs had relapsing illness and died or were euthanized by

2 years of age from progressive systemic amyloidosis and renal failure.

Necropsies were performed on three dogs, two of which had glomerular

amyloidosis and widespread evidence of vasculitis. The history, signs, and

close association with immunization suggested that juvenile onset

polyarthritis and subsequent amyloidosis in these Akitas may have been an

autoimmune response triggered by the viral antigens or other components of

vaccines. 3 The vaccine related history was reviewed for 129 puppies

belonging to the family of Akitas discussed above. Polyvalent MLV vaccine

was given to 104 of them, with 10 (9.8%) puppies showing adverse reactions

and death. Another six puppies received a polyvalent all killed vaccine

product (no longer commercially available) with no reactors, and 19 puppies

received homeopathic nosodes initially followed by killed canine parvovirus

(CPV) vaccine, with one reactor that died and one that became ill but

survived. 3 A genetic basis for immune mediated diseases and

immunodeficiencies states is well known. 1,2,12,13,15,17,18 The mechanism

for triggering immune mediated disease is poorly understood, but

predisposing factors have been implicated when genetically susceptible

individuals encounter environmental agents that induce nonspecific

inflammation, molecular mimicry, or both. 3,17 The combined effects of these

genetic and environmental factors override normal self tolerance and are

usually mediated by T cell imbalance or dys regulation. 17 Since the modern

Akita arose from a relatively small gene pool, understanding the potential

environmental triggers of juvenile onset IMPA has immediate importance.

Numerous agents have been implicated, including drugs, vaccines, viruses,

bacteria, chemicals, and other toxins. 13,10,11 Although the littermates

from affected families typically end up in different locales, all undergo

relatively standardized immunization procedures at a similar age.

Vaccine Associated Disease in Young Weimaraners 

The Weimaraner breed appears to be especially prone to both immune

deficiency and autoimmune diseases, which have been recognized with

increasing frequency in related members of the breed over the past 15 years.

3 Autoimmune thyroiditis leading to clinically expressed hypothyroidism is

probably the most common of these disorders, along with 

vaccine associated HOD of young Weimaraners. 2,3,17 During a 2year period

(19861988), Couto evaluated 170 related Weimaraners, including affected

puppies and their relatives, and the findings were relayed in a breed

newsletter as discussed in an earlier reference. 3 Clinical signs of the

affected dogs included high fevers, polyarthritis with pain and swelling

typical of HOD, coughing and respiratory distress from pneumonia, enlarged

lymph nodes, diarrhea, pyoderma, and mouth ulcers. In most cases, clinical

signs were first detected shortly after vaccination with a second dose of

polyvalent MLV vaccine when the puppies were between 2 and 5 months of age.

This author has studied more than 60 Weimaraners with vaccine associated

disease. In 24 cases described in a previous article, 3 the mean age of

onset of clinical signs was 13.5 weeks, with a mean reaction time of 10.5

days post vaccination. Males were predominantly affected. All affected

puppies showed high spiking fevers, cyclic episodes of pain, and

polyarthritis (HOD)Ì a group of signs identical to those of the affected

young Akitas described previously. Most affected puppies also showed

leukocytosis (with neutrophilia or neutropenia), diarrhea, lethargy,

anorexia, and enlarged lymph nodes. Some puppies also had levels of

immunoglobulin A, immunoglobulin M, or both below those expected for their

age, and one puppy had immunoglobulin G (IgG) deficiency as well. Other

signs included coughing, pneumonia, depression, seizures or ‰spaced out‰

behavior, refusal to stand or move, and hyperesthesia („ walking on

eggshells‰). The outcome for half of these cases was good (12 of the 24 are

healthy adults), although two died, three were euthanized as puppies, and

three remained chronically ill as adults. Another four cases were lost to

follow up. 

Management of this clinical syndrome is best accomplished with an initial

dose of parenteral corticosteroids followed by a tapering course of

corticosteroids over 4 to 6 weeks. Systemic broad spectrum antibiotic may be

given prophylactically, and vitamin C (500 to 1,000 mg daily) can be

included to promote immune support. Recurring episodes are treated by

increasing the corticosteroid dosage for a few days until the flare up has

subsided. The response to initial corticosteroid treatment is always

dramatic, with fever and joint pain usually subsiding within a matter of

hours. 

Serological titers for canine distemper virus (CDV) and CPV were determined

in 19 of the 24 affected Weimaraner puppies, and all were adequate. Upon

reaching adulthood, serum antibody titers were reevaluated, and detectable

CDV and CPV specific IgG persisted. Several of these dogs have subsequently

developed hypothyroidism and are receiving thyroid replacement. 3,4,17 Thus,

to avoid recurrence of adverse effects, which has been shown to be even more

severe if another vaccine booster is given, serological titers for CDV and

CPV are measured. 7 Another approach recommended by Weimaraner breeders and

this author is to modify the vaccination protocol, especially for puppies

from families known to have experienced adverse vaccine reactions. Examples

would be to limit the number of antigens used in the vaccine series to those

infectious agents of most clinical concern (i. e., CDV, CPV, and rabies

virus), separating these and other antigens by 2to 3 week intervals, and

giving rabies vaccine by itself at 6 months of age. A booster series is

administered at 1 year by separating the CDV, CPV, rabies virus, and other

vaccine components, where possible, and giving them on separate visits at

least 2 weeks apart. Thereafter, serological antibody titers can be measured

(except for those vaccines required by law, unless a specific exemption is

made on an individual case basis). 

Recommendations 

Practitioners should be encouraged during the initial visit with a new puppy

owner or breeder to review current information about the breed‚s known

congenital and heritable traits. Several databases, veterinary textbooks,

and review articles contain the relevant information to assist here. 2 For

those breeds at increased risk, the potential for adverse reactions to

routine vaccinations should be discussed as part of this wellness program.

Because breeders of atrisk breeds have likely alerted the new puppy buyer to

this possibility, we should be mindful and respectful of their viewpoint,

which may be more informed than ours about a specific breed or family issue.

To ignore or dismiss these issues can jeopardize the client patient

relationship and result in the client going elsewhere for veterinary

services or even turning away from seeking professional care for these

preventive health measures. As a minimum, if we are unaware of the

particular concern expressed, we can research the matter or ask the client

for any relevant scientific or medical documentation. The accumulated

evidence indicates that vaccination protocols should no longer be considered

as a „one size fits all‰ program. 

For these special cases, appropriate alternatives to current vaccine

practices include: measuring serum antibody titers; avoidance of unnecessary

vaccines or over vaccinating; using caution in vaccinating sick, very old,

debilitated, or febrile individuals; and tailoring a specific minimal

vaccination protocol for dogs of breeds or families known to be at increased

risk for adverse reactions. 3,58 Considerations include starting the

vaccination series later, such as at 9 or 10 weeks of age, when the immune

system is more able to handle antigenic challenge; alerting the caregiver to

pay particular attention to the puppy‚s behavior and overall health after

the second or subsequent boosters; and avoiding revaccination of individuals

already experiencing a significant adverse event. Littermates of affected

puppies should be closely monitored after receiving additional vaccines in a

puppy series, as they, too, are at higher risk. Altering the puppy

vaccination protocol, as suggested previously for the Weimaraner, is also

advisable. 

Following these recommendations may be a prudent way for our profession to

balance the need for individual patient disease prevention with the ageold

physician‚s adage, forwarded by Hippocrates, of „to help, or at least do no

harm.‰ 

References 

1. Dodds WJ. Immune mediated diseases of the blood. Adv Vet Sci Comp Med

1983; 27: 163196. 

2. Dodds WJ. Estimating disease prevalence with health surveys and genetic

screening. Adv Vet Sci Comp Med 1995; 39: 2996. 

3. Dodds WJ. More bumps on the vaccine road. Adv Vet Med 1999; 41: 715732. 

4. Hogenesch H, AzconaOlivera J, ScottMoncrieff C, Snyder PW, Glickman LT.

Vaccineinduced autoimmunity in the dog. Adv Vet Med 1999; 41: 733744. 

5. Schultz R. Current and future canine and feline vaccination programs. Vet

Med 1998; 93: 233254. 

6. Tizard I. Risks associated with use of live vaccines. J Am Vet Med Assoc

1990; 196: 18511858. 

7. Twark L, Dodds WJ. Clinical use of serum parvovirus and distemper virus

antibody titers for determining revaccination strategies in healthy dogs. J

Am Vet Med Assoc 2000; 217: 10211024. 

8. Tizard I, Ni Y. Use of serologic testing to assess immune status of

companion animals. J Am Vet Med Assoc 1998; 213: 5460. 

9. Phillips TR, Jensen JL, Rubino MJ, Yang WC, Schultz RD. Effects of

vaccines on the canine immune system. Can J Vet Res 1989; 53: 154 160. 

10. Duval D, Giger U. Vaccineassociated immunemediated hemolytic anemia in

the dog. J Vet Intern Med 1996; 10: 290295. 

11. Cohen AD, Shoenfeld Y. Vaccineinduced autoimmunity. J Autoimmun 1996; 9:

699703. 

12. May C, Hammill J, Bennett, D. Chinese shar pei fever syndrome: a

preliminary report. Vet Rec 1992; 131: 586587. 

13. Day MJ, Penhale WJ. Immunemediated disease in the old English sheepdog.

Res Vet Sci 1992; 53: 8792. 

14. Dougherty SA, Center SA. Juvenile onset polyarthritis in akitas. J Am

Vet Med Assoc 1991; 198: 849855. 

15. ScottMoncrieff JCR, Snyder PW, Glickman LT, Davis EL, Felsburg PJ.

Systemic necrotizing vasculitis in nine young beagles. J Am Vet Med Assoc

1992; 201: 15531558. 

16. Wilbur LA, Evermann JF, Levings RL, et al. Abortion and death in

pregnant bitches associated with a canine vaccine contaminated with blue

tongue virus. J Am Vet Med Assoc 1994; 204: 17621765. 

17. Happ GM. ThyroiditisÌ a model canine autoimmune disease. Adv Vet

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