The Current Status of Canine Vaccinations:

Are We Vaccinating Dogs with Too Many Vaccines Too Often?
Cynda Crawford, DVM, PhD
University of Florida

Since the 1950’s, veterinary medicine has done an excellent job in educating pet owners on the importance of vaccination. There is no debate over the health benefits that millions of dogs have derived from vaccination against distemper, parvovirus, infectious hepatitis, and rabies. The decrease in number of human, canine, and farm animal cases of rabies in recent years, despite an increasing incidence in wildlife, is largely attributable to vaccination of dogs.1
Vaccination not only protects the individual dog, but also decreases disease prevalence and transmission in the canine population as a whole, even if some of the dogs are not vaccinated. For example, rabies is not effectively transmitted if more than 70 percent of the canine population is vaccinated.1
Outbreaks of disease occur when the proportion of immune individuals decreases below a threshold, either because of decreasing immunity in vaccinated dogs or decreased number of dogs vaccinated. Thus, the population’s immunity to an infectious agent needs to be maintained by vigilant vaccination of individuals at risk for exposure and transmission of disease.
More than 20 years ago, the American Veterinary Medical Association (AVMA) recommended annual revaccination of all dogs, a practice still common today. This recommendation was based on the assumption that immunity would dwindle in some dogs, so that frequent revaccination of all dogs was required to insure immunity in the population.

Recommendation for annual revaccination of all dogs with multivalent or combo vaccines assumes that every dog is at significant risk for exposure to every infectious agent in the vaccine, and that each agent in the vaccine will stimulate the same degree of immunity that lasts the same amount of time.1 Today,we know that these assumptions are neither rational nor scientifically justified, but are convenient for the veterinarian and pet owner alike.
Vaccination should not be a regimented, one-fits-all procedure.1 The objective of vaccination is simply to give the right vaccine at the right time to the right individual to protect that individual from an infectious disease. To accomplish this objective, each dog should be evaluated with regard to age, lifestyle, disease prevalence in the community, potential for exposure to infected dogs and environments, and the severity of clinical disease, if any, after infection.2 The benefit of vaccination is questionable if the potential for exposure is limited by lifestyle, the prevalence of disease in the community is low, and the clinical disease is either unapparent or mild.

Vaccination is a medical procedure, and as such, requires individual assessment of each patient. Fortunately, the most common effect of vaccination is stimulation of a protective immune response. Despite the intended benefits, vaccination does carry with it attendant risks. Now, a growing awareness of vaccine-related health problems is motivating veterinarians and pet owners alike to question the benefit of annual revaccination or boosters for adult dogs. The concern, controversy, and confusion centers around the question Are we vaccinating dogs with too many vaccines too often? 2

Vaccine Types

There are three types of vaccines: killed vaccines, modified live vaccines, and recombinant vaccines.1,3
Vaccines that contain killed viruses or bacteria also contain an adjuvant, usually aluminum hydroxide, to nonspecifically boost the immune response to the vaccine. The advantages of killed vaccines include lack of replication in the host, no chance of reversion of the infectious agent to virulence, and safer for use in dogs that are immunosuppressed or in breeding bitches housed in contact with neonates. The disadvantages include a higher incidence of adverse reactions to the killed organisms suspended in adjuvant, formation of lower amounts of antibody that do not remain at protective levels for very long, and requirement for frequent vaccinations to boost the immunity to protective levels. In addition, killed vaccines must be administered by intramuscular or subcutaneous injection. Examples of killed vaccines commonly used in dogs include those for coronavirus, leptospirosis, kennel cough, Lyme disease, giardia, and rabies.
Modified live vaccines (MLV) contain live viruses or bacteria whose virulence has been
modified to allow replication in the host without causing disease. These vaccines simulate natural immune responses in that they stimulate rapid humoral and cell-mediated immunity that is sustained at high levels for long periods of time. Some of these vaccines can be given at the site where the pathogen normally invades the body, such as the nostrils, thus inducing a localized immune response that acts quickly to prevent invasion. Examples of commonly used modified live vaccines in dogs include those for distemper, parvovirus, canine infectious hepatitis, parainfluenza, and kennel cough. Both killed and modified live vaccines can be monovalent or multivalent. Monovalent vaccines contain only one infectious agent, whereas multivalent vaccines contain two or more.
Recombinant vaccines are genetically engineered vaccines created by inserting selected genes from an infectious agent into a nonpathogenic carrier agent that serves as a production factory. The proteins made from the selected genes are those that are critical in stimulating protective immunity to the infectious agent, and thus focus the immune response. The proteins can be harvested after production by the carrier agent and used as a purified protein vaccine, with or without adjuvant. An example of this type of recombinant vaccine is the new one for Lyme disease. Alternatively, a nonpathogenic virus into which the selected genes of the pathogen have been inserted can serve as the actual vaccine. Replication of the nonpathogenic carrier virus in the dog produces the pathogen proteins that induce a protective immune response. An example of this is the new recombinant vaccine for canine distemper.

Duration of Vaccine-Induced Immunity

Vaccine manufacturers in the United States are required by the USDA to conduct efficacy and safety studies for their vaccines prior to licensure.1 The efficacy studies are challenge studies, the gold standard for demonstrating protective immunity provided by a vaccine. In challenge studies, non-vaccinated and vaccinated dogs are exposed to the virulent organism at various times after vaccination to determine the extent and duration of protection against disease. The manufacturer is not required to establish the full duration of immunity for the vaccine, but only to provide documentation of what they claim on the label, hence the recommendation for annual revaccination.1 However, minimum duration of immunity challenge studies are required for all rabies vaccines, and for all new vaccines using antigens that were not in use prior to 1995.1

Vaccines produced by different companies may induce different durations of immunity against the same diseases. Trials to determine the duration of immunity beyond that of one year that would meet USDA guidelines can be cost-prohibitive. However, recent challenge studies performed by independent research groups have demonstrated that the minimum duration of immunity induced by modified live virus vaccines for distemper, parvo, canine infectious hepatitis, and parainfluenza is actually five to seven years, not one year!1 Furthermore, annual revaccination in these challenge studies did not provide any additional benefit in terms of the strength of the humoral immune response elicited, improved resistance to disease, or extension of the duration of immunity.

Thus, based on duration of immunity, annual revaccination of adult dogs is probably not necessary for protection against distemper, parvovirus, canine infectious hepatitis, and parainfluenza.1, 2

Who Should be Vaccinated with What and When?
Puppies less than six months old are more susceptible to the common infectious diseases than adults, and therefore are the primary target population for vaccination.1 In the US, the incidence of clinical disease from distemper, infections hepatitis, and parvovirus in dogs older than one year of age is virtually zero.1
In 2001, the American Veterinary Medical Association Council on Biologic and Therapeutic Agents (COBTA) presented guidelines for vaccination of dogs.2 The guidelines emphasized that there are inadequate data at this time to support a single best vaccination protocol, so veterinarians should perform a risk to benefit analysis for the use of each vaccine in each patient. The guidelines divide currently available vaccines into core and non-core. Core vaccines are selected based on the prevalence of the infectious agent in the environment, the severity of the clinical disease that results from infection, the ease with which the infectious agent is transmitted between animals, and the zoonotic potential. Core vaccines include canine distemper, parvovirus, infectious hepatitis virus, and rabies. Non-core vaccines are those that are useful in situations where the risk of exposure is high and disease can be debilitating. These include vaccines for leptospirosis, parainfluenza, coronavirus, kennel cough, Lyme disease and giardia.

High levels of maternal antibodies acquired from ingestion of colostrums protect puppies from disease for the first six to eight weeks of life. After six to eight weeks of age, a window of susceptibility to infection is created because maternal antibodies are high enough to interfere with the vaccine-induced response, but not high enough to protect the pup from infection and disease.1 This maternal antibody blockade is the most common cause of vaccine failure in puppies. Therefore, immunizations are repeated at timed intervals during the first four to six months of the puppy’s life to insure development of a protective immune response. The pediatric series include the core vaccines for distemper, parvovirus, and infectious canine hepatitis starting with an initial immunization at six to eight weeks of age, followed by boosters every three to four weeks until 16 weeks old. Certain breeds have a higher frequency of individuals that do not develop vaccine-induced antibody titers during the routine pediatric series. These breeds include the Rottweiler, Doberman Pinscher, Labrador Retriever, Alaskan sled dog, Pomeranian, and American Staffordshire Terrier.4 For puppies of these breeds, boosters are recommended every three to four weeks until 24 weeks of age.

The most popular core vaccines are modified live vaccines that contain a combination of distemper virus, canine adenovirus type 2 for protection against infectious hepatitis, parvovirus and parainfluenza virus (DHPP or DA2PP). Contrary to popular belief, combining these viruses into multivalent vaccines does not alter the immune response to each ; no scientific study has shown that one virus suppresses the immune response to the other viruses given at the same time, so it is not necessary to alternate vaccination with each separately.1 Several potentiated monovalent vaccines are available for parvovirus. Potentiated vaccines contain very high titers of parvovirus, and are most effective in overcoming the maternal antibody blockage in young puppies. The original parvovirus, CPV2, has been replaced over the years by two antigenic variants or biotypes called CPV2a and CPV2b. The CPV2b biotype is more prevalent in the US, while the CPV2a is more prevalent in Europe. Most licensed parvovirus vaccines still contain the original CPV2 virus, but the induced immunity is cross protective against both biotypes.1, 5 A recently marketed recombinant vaccine for distemper (Recombitek CDV, Merial) uses the canarypox virus as a vector for a distemper virus gene that codes for a protein associated with protective immune responses.3 The vaccine is effective but the minimum duration of immunity beyond one year has not been established.

The last core vaccine administered during the pediatric series is rabies. The rabies vaccine is the only one that is legally required due to the health threat to humans. Most states require an initial vaccination at 12-16 weeks of age, followed by a booster one year later. State laws vary on revaccination intervals for adult dogs, with intervals ranging from one to three years. Rabies vaccines contain large amounts of killed virus suspended in adjuvant, and have a minimum duration of immunity of one year or three years.

Based on the long duration of immunity for the core vaccines against distemper, canine infectious hepatitis, and parvovirus, Dr. R.D. Schultz at the University of Wisconsin proposed that a more ideal vaccination program would be one in which dogs were revaccinated one year after completion of the pediatric series, then at three-year intervals thereafter.1 However, revision of current protocols for these vaccines should not be done without accurate epidemiological data about the prevalence of each disease in the community, and a careful risk assessment for each dog.

Non-Core Vaccines
Non-core vaccines are recommended only for dogs in situations where the risk of exposure is high and the disease can be debilitating.2 These include vaccines for coronavirus, leptospirosis, parainfluenza, kennel cough, Lyme disease, and giardia. Most non-core vaccines require annual revaccination due to their short duration of immunity. In addition, most of these vaccines contain killed organisms suspended in adjuvant, which increases the risk for vaccine-associated reactions.
Canine coronavirus can cause clinical disease in pups less than six weeks old, but most are protected by maternal antibodies.1 The clinical disease is very mild compared to parvo, and unlike parvo, is confined to the intestinal tract without any systemic involvement. Concurrent infection with coronavirus can contribute to the severity of clinical disease in puppies infected with parvovirus, but vaccination of puppies against parvovirus will prevent disease from both.1
Therefore, it is difficult to rationalize the use of a coronavirus vaccine, but more doses of multivalent vaccines containing killed coronavirus are sold than those without, indicating that most pups and adult dogs are routinely vaccinated anyway. The vaccine, which contains killed virus in adjuvant, may be most useful for brood bitches in kennels where diarrhea is a problem in young pups prior to weaning. Vaccines containing killed coronavirus combined with killed leptospirosis bacteria targeted for use in puppies should not be used due to increased frequency of hypersensitivity reactions.1
Canine leptospirosis is a bacterial infection that causes kidney and liver failure in dogs of all ages. The bacterial species, Leptospira, has several different variants, called serovars, which are antigenically distinct from each other, thus antibodies to one will not protect against infection with other serovars. Vaccines for leptospirosis contain killed bacteria from the L. canicola and L. icterohemorrhagie serovars. The killed bacteria are usually incorporated into multivalent vaccines containing modified live distemper virus, parvovirus, adenovirus, and parainfluenza virus (DHLPP, DA2LPP). The killed bacteria suspended in adjuvant are responsible for many hypersensitivity reactions, particularly in Dachshunds and other small breeds, and only induce a short-lived immunity of six to eight months.1 However, widespread use of multivalent vaccines containing L. canicola and L. icterohemorrhagie for many years has been credited with the reduced prevalence of these two serovars in the canine population. New serovars, such as L. Pomona and L. grippotyphosa have now emerged as the predominant cause of canine leptospirosis, and the old vaccines do not induce protective immunity to these bacteria.1
Recently, Fort Dodge has developed a new killed vaccine that contains L. Pomona and L. grippotyphosa for use in dogs at risk for exposure, but the duration of immunity is still less than 12months.1
Kennel cough, or infectious tracheobronchitis, is an upper respiratory tract disease caused by Bordetella bronchiseptica bacteria alone, or in concert with a variety of viruses such as parainfluenza, distemper, canine adenovirus type 2, and herpesvirus. The intranasal vaccine contains live avirulent B. bronchiseptica combined with modified live parainfluenza virus. This vaccine rapidly stimulates mucosal and cell-mediated immunity in the upper respiratory tract where the pathogens enter the body, so that vaccination three to five days prior to anticipated exposure provides protection. The intranasal vaccine can also be given to pups after three weeks of age, and is not subject to the maternal antibody blockade. However, replication of the attenuated bacteria and virus in the upper respiratory tract can cause mild clinical signs that resolve in a few days. The parenteral vaccines given by injection contain killed B. bronchiseptica, and thus require boosters two to four weeks apart to generate protective levels of immunity. These killed vaccines induce systemic immune responses that contribute to protection of the respiratory tract without inducing a mild clinical disease like the modified live vaccine, but do cause more vaccine-associated hypersensitivity reactions.

Parenteral vaccines are safe to use in breeding bitches, but are subject to maternal antibody blockade when given to puppies. The duration of immunity for both the intranasal and parenteral vaccines is probably less than 12 months.1 It is generally thought that stimulation of local immunity in the respiratory tract with an intranasal vaccine is superior to use of parenteral vaccines. Others have proposed that protocols incorporating both types of vaccines are superior to either vaccine alone. A recent study6 found that administration of both the intranasal and parenteral vaccine once each in sequence afforded better protection and less severe clinical signs from B. bronchiseptica challenge than either vaccine alone.
Lyme disease is caused by Borrelia burgdorferi bacteria transmitted by tick bites. The vast majority (99 percent) of cases are in the northeastern, middle Atlantic and upper Midwester n states. Vaccination is recommended for dogs in these endemic areas, but not for dogs in areas of low prevalence, such as the southeast.1 The Lyme vaccine contains killed bacteria suspended in adjuvant, and has produced postvaccinal lameness in dogs. In addition, the vaccine contains limited strains of the bacteria and may not induce cross protective immunity to other strains that cause disease. A new recombinant vaccine licensed for use in dogs contains purified bacterial out surface protein A (OspA) instead of whole bacteria, does not have an adjuvant, and challenge studies have shown a minimum duration of immunity of one year.3
Giardia is a protozoan that infects the gastrointestinal tract of birds and mammals worldwide, and causes explosive diarrhea, gas, and pruritic skin lesions in dogs. The infection responds to medical therapy, but reinfection rates are high because the infectious cysts shed in fecal material persist on the dog and in the environment. There is a new killed vaccine (GiardiaVax, Fort Dodge) licensed for use in dogs and pups older than six weeks that contains inactivated giardia trophozoites. Challenge studies have shown that the vaccine stimulated a strong antibody response within three weeks, and vaccinated dogs were less severely affected clinically and shed cysts for a shorter time compared to non-vaccinated dogs1. The decreased shedding of cysts was maintained for up to one year. In a clinical trial supported by the manufacture7, six pet dogs with chronic giardia infections for months to years received two doses of the vaccine given three weeks apart, which eliminated clinical signs and shedding of cysts with two to eight weeks. However, in a recent independent study8 in which digs infected with giardia were treated medically with or without the vaccine, medical treatment alone was effective without the vaccine, as long as the dogs were bathed and put in a different environment. The vaccine did not prevent recurrence of infection in dogs that were not bathed and moved to a different environment.

Assessment of Immune Status by Antibody Titers
One method to assess the adequacy of humoral immunity induced by vaccination is measurement of antibody titers to the infectious agent vaccinated against. The vaccine-induce antibody titer is compared to a standard titer associated with prevention of infection. Antibody titers are increasingly recommended as an objective method for determining the need for revaccination. However, antibody titers do not necessarily correspond to protection against disease.1, 2 A high antibody titer does not guarantee immune protection, and a low or negative antibody titer does not mean loss of immunity and susceptibility to infection. Certain breeds have higher numbers of individuals that do not develop antibody titers after vaccinations. These breeds include the Rottweiler, Doberman Pinscher, Labrador Retriever, Alaskan sled dog, Pomeranian, and American Staffordshire Terrier.4 Yet, dogs in these breeds with no or low antibody titers remain healthy, presumably because of vaccine stimulation of other important immune system compartments such as cell-mediated immunity, mucosal immunity, and immune memory cells, all of which cannot be accurately or practically measured at this time. Unfortunately, there are no standardized tests for measuring antibody titers with reliable interpretations, so that submission of a serum sample to three different labs most likely would yield three different results with three different interpretations.2

In a recent study4, serum antibody titers to distemper and parvovirus were measured in 1,441 dogs of various ages and breeds located across the US and Canada. In this population, more than 95 percent had adequate titers to distemper and parvo. For the 468 dogs with known vaccination histories, the interval of time after the last vaccination was one to two years for the majority (60 percent), two to seven years for 30 percent, and less than one year for ten percent. Based on these results, the authors concluded that annual revaccination of adult dogs may not be necessary, and that an acceptable alternative approach is antibody titer screening to determine the need for vaccination on an individual basis. An alternate vaccination protocol has also been proposed for puppies from families with known genetic predisposition to adverse vaccine reactions or immune-mediated diseases.9 This protocol suggests using only monovalent vaccines for distemper and parvovirus with alternating administration every three to four weeks until the puppy has received a total of three doses of each vaccine. The vaccines are boosted at one year of age, again using monovalent vaccines given at least two weeks apart, followed by measurement of antibody titers to determine future need for revaccination.

Adverse Vaccine Reactions
Just as no vaccine is 100 percent effective in preventing disease, no vaccine is 100 percent free from causing an adverse reaction. An adverse event is defined as any undesirable consequence, including illness or a reaction, after the use of a vaccine, whether or not a cause-and-effect relationship can be established.2 The most commonly recognized adverse reactions are the nonspecific reactions of immune system stimulation, including fever, anorexia, and stiffness for 24-36 hours after vaccination.10 Another common systemic reaction, most frequently reported with killed vaccines, is immediate hypersensitivity of anaphylaxis, indicated by urticaria (hives) and pruritis of the face and ears followed by vomiting and/or diarrhea in some dogs.10 These signs can occur immediately after vaccination or several hours later. Local reactions to vaccines with adjuvants include swelling, pain, lumps, and hair loss at the vaccine site. Other reactions include abortions and birth defects due to vaccination of pregnant dogs, and illness in neonates exposed to dogs recently vaccinated with modified live vaccines that are shedding the vaccine viruses into the environment.

For most currently available vaccines, the benefits derived far outweigh the risks for an adverse event when vaccination is performed in accordance with published standards.10 With the technology available today, there is no way to accurately predict what vaccine will pose a threat to which dog and when.
Manufacturers of human vaccines are required to list on the vaccine label the type and frequency of adverse events that occurred during safety trials.10 There are approximately 12,000 reports of adverse events annually for human vaccines, all of which must be forwarded to the FDA, the federal agency that regulates drugs and vaccines for humans.10 In contrast, animal vaccine manufacturers are neither required to list possible adverse reactions on vaccine labels, nor keep records of adverse events reported directly to them, nor forward reports to the USDA, the federal agency that regulates drugs and vaccines for animals.10 There are approximately 10,000 reports of adverse events associated with animal vaccines annually in the US, but the vast majority of these are communicated directly to the manufacturers.10 However, veterinarians and pet owners can report concerns directly to the USDA or to the Veterinary Practitioners Reporting Program, which is a volunteer watchdog organization that forwards reports of adverse reactions to the USDA, vaccine manufacturer, and the AVMA in an effort to protect animal health.
One of the best-developed surveillance schemes in the world for monitoring adverse reactions to veterinary vaccines is in the United Kingdom. In contrast to the US, vaccine manufacturers in the UK are legally required to record reports of adverse reactions and submit the reports to a regulatory agency.11 The Veterinary Products Committee, an independent group that gives advice on the safety, quality, and efficacy of veterinary vaccines to the regulatory agency, recently published a report on vaccine-associated adverse events in the UK.11 The overall annual incidence of adverse events in dogs from 1995 – 1999 was less than 0.1 percent per 10,000 doses of vaccines sold, which is similar to that reported in Australia. Toy breeds and puppies less than six months old had the highest incidence of the five-year reporting period. Anaphylaxix reactions were the most common type reported. The group concluded that there are insufficient scientific data to warrant changing revaccination intervals from that already approved by the regulatory agencies, and that the very low incidence of adverse reactions sdtronly supports continued vaccination. However, the group strongly emphasized that dogs should be individually assessed with regard to the need for each vaccine as well as the frequency of administration.

Immune-Mediated Diseases and Vaccinosis
There is increasing evidence suggesting that vaccination, particularly overvaccination, is associated with development of immune-mediated disorders and chronic diseases, or vaccinosis, in individuals that are genetically predisposed. Certain breeds appear more genetically predisposed to developing adverse reactions and immune-mediated diseases following vaccination, including the Old English Sheepdog, Akita, American Cocker Spaniel, Standard Poodle, Scottish Terrier, Shetland Sheepdog, Shih Tzu, Vizsla, Weimaraner, Irish Setter, Doberman Pinscher and Dachshund.9 There are two published studies12, 13 that linked vaccination and development of immune-mediated hemolytic anemia. More recent reports9, 14 have suggested vaccine-induced development of Hypertrophic Osteodystrophy in Weimaraner puppies that were genetically predisposed to the disease. Other reports linking vaccination to development of joint diseases, neurological diseases, and thyroid disease are largely anecdotal, and await rigorous scientific validation. To date, there are no controlled scientific studies that prove a cause and effect relationship between vaccination and development of immune-mediated diseases or chronic diseases.10, 11
Due to concern about vaccination overload of the immune system with development of autoimmune diseases and vaccinosis, there has been a proliferation of anti-vaccination websites offering alternatives to conventional vaccinations. One of the alternatives is nosodes which are products prepared from infected tissues or discharges given orally.2 General recommendations for use of nosodes include administration orally for three days the first week, then once weekly for three weeks, then once monthly for six months, then every six months thereafter. The dose is three drops for small dogs and six drops for large dogs. The nosode does not cause disease because of homeopathic dilution, where the product is diluted enough that the amount of infectious material remaining is too little to cause disease. There has been only one controlled study on the efficacy of nosodes for protection against disease. This study2 examined a nosode for parvovirus and found that 100 percent of the non-vaccinated as well as vaccinated puppies became infected when challenged with the virus.

Are we vaccinating dogs with too many vaccines too often? Probably. No doubt, there will be changes in the who, what, when and how for canine vaccinations. In general, canine vaccines are effective and safe, with benefits that far outweigh the risks. However, more rigorous controlled studies are needed on vaccine efficacy, duration of immunity, and safety to point out a scientifically sound direction for change. Change is hard, and human nature resists change unless there is compelling evidence to do so. It is important to remember that the overall goal of vaccination is protection of the population as a whole, which can be achieved by vaccinating more dogs, but vaccinating each dog less. To date, the best protocol for vaccination is individual assessment of every dog with regard to age, health status, risk of exposure to the infectious agent, prevalence of the infectious agent in the community, and severity of illness caused by the infectious agent.

Selected References
1. Greene CE, Schultz RD, Ford RB. Canine Vaccination. In: North American Veterinary
Clinics 2001. Ford RB, ed. 31(3): 473-492.
2. Ford RB. Vaccines and vaccination: The strategic issues. In: North American Veterinary
Clinics 2001. Ford RB, ed. 31(3): 439-453.
3. Van Kampen KR. Recombinant vaccine technology in veterinary medicine. In: North American Veterinary Clinics 2001. Ford RB, ed. 31(3): 535-538.
4. Twark L, Dodds WJ. Clinical use of serum parvovirus and distemper virus antibody titers for determining revaccination strategies in healthy dogs. JAVMA 2000; 217: 1021-1024.
5. Pratelli A, Cavalli A, Martella V, et al. Canine parvovirus (CPV): comparison of neutralizing antibody responses in pups after inoculation with CPV2 or CPV2b modified live virus vaccine. Clin and Diag Lab Immunol 2001; 8:612-615.
6. Ellis JA, Haines DM, West KH, et al. Effect of vaccination on experimental infection with Bordetella bronchiseptica in dogs. JAVMA 2001; 218:367-375.
7. Olson ME, Hannigan CJ, Gaviller PF, et al. The use of a Giardia vaccine as an
immunotherapeutic agent in dogs. Can Vet J 2001; 42:865-868.
8. Payne P, Ridley RK, Dryden MW, et al. Efficacy of a combination febantel-praziquantel-pyrantel product, with or without vaccination with a commercial Giardia vaccine, for treatment of dogs with naturally occurring giardiasis. JAVMA 2002; 220:330-333.
9. Dodds WJ. Vaccination protocols for dogs predisposed to vaccine reactions. J Am Anim Hosp Assoc 2001; 37:211-214.
10. Meyer EK. Vaccine-associated adverse events. In: North American Veterinary Clinics 2001.Ford RB, ed. 31(3):493-514.
11. Gaskell RM, Gettinby G, Graham SJ, et al. Veterinary Products Committee working group report on feline and canine vaccination. Vet Rec 2002; 150:126-134.
12. David D, Giger U. Vaccine-associated immune-mediated hemolytic anemia in the dog. JVIM 1996; 10:290-295.
13. Hogenesch H, Azcona-Olivera J, Scott-Moncrieff C, et al. Vaccine-induced autoimmunity in the dog. Adv Vet Med 1999; 41:733-747.
14. Harrus S, Wainer T, Aizenberg I, et al. Development of Hypertrophic Osteodystrophy and antibody response in a litter of vaccinated Weimaraner puppies. J Small Animal Practice 2002; 43:27-31.

Dog Owners and Breeders Symposium
July 27, 2002
University of Florida
College of Veterinary Medicine