SPECIAL Report

Report of the American Animal
Hospital
Association (AAHA) Canine Vaccine
Task Force: 2003 Canine Vaccine
Guidelines, Recommendations,
and Supporting Literature
 

Max Appel, DVM, PhD

Ralph Barrett, DVM,
Diplomate ACVIM

Leland E. Carmichael,
DVM, PhD,
Diplomate ACVM

Henry Childers, DVM,
Diplomate ABVP

Susan Cotter, DVM,
Diplomate ACVIM

Autumn Davidson, DVM,
Diplomate ACVIM

Richard Ford, DVM, MS,
Diplomate ACVIM

Dan Keil, DVM, PhD,
Diplomate ACVM

Michael Lappin, DVM, PhD,
Diplomate ACVIM

Ronald D. Schultz, PhD,
Diplomate ACVM

Eileen Thacker, DVM,
Diplomate ACVM

Janice L. Trumpeter, DVM

Link Welborn, DVM,
Diplomate ABVP

This document was developed by the American Animal Hospital Association through a collaborative effort among Task Force members (see Appendix 1) to aid practitioners in making decisions about appropriate care of their canine patients with respect to currently available vaccines.

Limited published scientific information exists on duration of vaccine immunity. Therefore, these guidelines and recommendations are based on limited scientific evidence but are supported by consensus and expert opinion as well as clinical experience.

These guidelines and recommendations should not be construed as dictating an exclusive protocol, course of treatment, or procedure. Variations in practice may be warranted based on the needs of the individual patient, resources, and limita-tions unique to each individual practice setting.
This report was funded in part by the AAHA Foundation.

While significant efforts have been expended and real-ized with respect to vaccine efficacy and safety, their impact on product use (specifically vaccine protocols) has largely been ignored until recently; this despite early rec-ommendations for less frequent revaccination. In 1978, “an ideal vaccination program” was recommended where dogs and cats would be vaccinated as puppies and kittens and then revaccinated at 1 year of age and every third year thereafter.1 In 1998, the American Association of Feline Practitioners (AAFP) debated and subsequently endorsed this same recommendation for feline core vaccines; the AAFP recommendations were updated in 2000. 2 Also in 1998, recommendations from a group of canine vaccine experts were published.3 They recommended revaccination with canine core vaccines no more than once every 3 years following initial booster revaccination at 1 year of age. This proposed vaccination program, and various iterations thereof, has been adopted to varying degrees by a growing part of the profession, but misunderstandings, misinforma-tion, and the conservative nature of the profession have slowed adoption of these protocols advocating decreased frequency of revaccination.

In 2002, the American Veterinary Medical Association (AVMA) updated their vaccine guidelines 4 after recogniz-ing that traditional guidelines were not compatible with the recommendations of a growing number of veterinary practi-tioners and experts in the fields of vaccinology and infec-tious diseases. Although many of these experts support triennial vaccination against core diseases, there is a rela-tive paucity of published scientific documentation to indi-cate that every 3 years is any more rational than every 2 years or any less rational than every 7 years. For that reason, the AVMA and AAHA guidelines intentionally allow room for individual veterinarians to apply them. Information (including discussions on core/noncore vaccines, immunol-ogy, DOI, vaccine production and licensing, adverse event reporting, and potential practice impact and opportunity) is provided in this report for veterinarians to review and use as they develop a vaccine program for their practices and their individual patients.

Many diseases we immunize against are ubiquitous. Many are serious and some even life threatening. Some are of limited demographic concern given the exposure risk for each patient. These factors have all been considered in developing the AAHA Canine Vaccine Guidelines and Rec-ommendations. In the end, each veterinarian must do what he or she determines to be in the best interest of the patient. Vaccination of individual animals produces not only indi-vidual immunity but also population or herd immunity. Since we have no readily available and reliable way to determine if each patient has developed an adequate immune response, we encourage the practice philosophy of vaccinating more patients while vaccinating each patient no more than needed.

Task Force Recommendations Regarding the Selection and Use of Canine Vaccine Antigens

Decisions on vaccine selection and use require a balance among disease incidence and severity, vaccine efficacy (including DOI) and safety, and the health, welfare, and lifestyle of the individual animal. When taking all these variables into account, it becomes apparent that a blanket or generic statement encompassing the use of all vaccine prod-ucts is impossible to make. However, based on the growing body of knowledge in the areas of vaccinology and immunology, general vaccine guidelines are appropriate and useful as a foundation upon which to make specific rec-ommendations for individual patients. The 2003 AAHA Canine Vaccine Guidelines and Recommendations are dis-cussed in the following sections as well as presented in an easy-to-reference table format [Table 1]. These guidelines are based on current knowledge with respect to disease inci-dence and severity and vaccine efficacy.

Vaccine Selection: Core (Recommended), Noncore (Optional), and Not Generally Recommended Canine Vaccines

Recommended or “core” vaccines are those that the com-mittee believes should be administered to all puppies (dogs <6 months of age) or dogs with an unknown vaccination history. The diseases involved have significant morbidity and mortality and are widely distributed. The committee believes this group of vaccines comprises canine distemper virus (CDV), CPV, canine adenovirus-2 (CAV-2), and rabies virus.

Optional or “noncore” vaccines are those that the com-mittee believes should be considered only in special cir-cumstances because their use is more dependent on the exposure risk of the individual animal. Issues of geographic distribution and lifestyle should be considered before administering these vaccines. In addition, the diseases involved are generally self-limiting or respond readily to treatment. The committee believes this group of vaccines comprises distemper-measles virus (D-MV), canine parain-fluenza virus (CPIV), Leptospira spp., Bordetella bronchi-septica, and Borrelia burgdorferi.

Vaccines identified as “not generally recommended” are those that the committee believes have little or no indi-cation. The diseases involved are either of little clinical sig-nificance or respond readily to treatment...<snip>

Table 1
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

A booster vaccination interval of 3 yrs among adult dogs is protective and reasonable.

A dose >4 wks after the last dose in this series will significantly increase the likelihood of sterile immunity \ with this product.

Does not routinely provide sterile immunity and may take longer to protect immunologically naive dogs. Therefore, not recommended where CDV is a serious threat for puppies (e. g., shelters, kennels, puppy/ pet stores).

Minimum demonstrated DOI for r CDV is 1 yr. Therefore, at present, annual revaccination is recommended A vaccination program that includes MLV- CDV vaccine for the initial vaccination followed by booster vaccinations with r CDV would provide excellent protection; revaccination with r CDV every 3 yrs would be reasonable in this scenario.

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Table 1 (cont'd)
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

Products with CPV- 2 regardless of genotype (i. e., CPV- 2, 2a, or 2b) all provide excellent protection against field isolates.

Annual vaccination recommended until DOI studies show longer than 1 yr of protection with the killed product.

When puppy is vaccinated with MLV and revaccinated at 1 yr with MLV, killed product could be used as booster >3 yrs.

Not recommended for animals at high risk for parvovirus (e. g., shelters, kennels, puppy/ pet stores).

Killed parvovirus products are susceptible to maternal antibody interference in puppies as old as 16- 18 wks of age

Two doses, 2- 4 wks apart (if using killed)

Upon completion of the initial series, and following a booster at 1 yr, revaccination once every 3 yrs is considered protective.

Table 1 (cont'd)
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

Note: The rabies (1- yr) vaccine is sometimes administered as the initial dose followed 1 yr later by administration of the rabies 3- yr vaccine. State, provincial, and local statutes may dictate otherwise.

One- yr rabies products should not be considered to cause fewer adverse reactions when given annually than 3- yr rabies products.

Note: Route of administration may not be optional. see product literature for details.

Note: The 3- yr rabies vaccine may be used as an alternative to the 1- yr rabies vaccine for initial and subsequent doses. Local statutes apply.

Note: The 3- yr rabies vaccine may be used as an alternative to the 1- yr rabies vaccine for initial and subsequent doses. Local statutes apply.

Note: The rabies 1- yr vaccine is sometimes administered as the

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Table 1 (cont'd)
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

Note: Route of administration may not be optional. see product literature for details.

Note: Administer IM only. MV does not effectively immunize if administered subcutaneously.

Parenteral. Upon completion of the initial series, and following a booster at 1 yr, revaccination once every 3 yrs is considered protective (DOI).

Parenterally administered vaccine is less effective than topically (intranasal) administered vaccine.

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Table 1 (cont'd)
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

(Also available with serovars grippotyphosa and pomona)

Do not administer to dogs <12 wks of age for optimal response.

Anecdotal reports from veterinarians and breeders suggest that the incidence of postvaccination reactions (acute anaphylaxis) in puppies (< 12 wks of age) and small- breed dogs is high. Reactions are most severe in young (< 9 wks of age) puppies. Routine use of the vaccine should be delayed until dogs are >9 wks of age. Older dogs are more likely to develop an optimal immune response than younger animals.

Minimum DOI based on challenge studies has been shown to be approximately 1 yr for serovars canicola and icterohaemorrhagiae; however, efficacy of the products can be low (< 75%).

DOI for serovars grippogyphosa and pomona are assumed to be up to 1 yr.

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Table 1 (cont'd)
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

For best results, if the product is used prior to 5- 6 wks of age, it should be given again after 6 wks of age.

If not vaccinated within the previous 6 mos, a booster is recommended 1 wk prior to known exposure (e. g., boarding, showing, etc.).

Note: Transient (3- 10 days) coughing, sneezing, or nasal discharge occurs in a small percentage of vaccinates. Antimicrobial therapy may be indicated to manage postvaccination upper respiratory signs (persistent cough and nasal discharge). DOI is believed to be approximately 10 mos for Bordetella bronchiseptica.

Note: Topically administered vaccines for canine infectious tracheobronchitis may provide a superior local immune response compared to parenterally administered vaccines.

This product has not been shown to provide any benefit not achieved with the intranasal Bordetella bronchiseptica plus canine parainfluenza virus in dogs that are receiving CAV- 2 parenterally.

Note: Topically administered vaccines for canine infectious tracheobronchitis may

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Table 1 (cont'd)
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

DOIs as noted above for individual vaccines.

Revaccinate just prior to start of insect (tick) season

Annually, just prior to start of insect (tick) season

Most authoritative papers recommend the r Lyme borreliosis vaccine over the killed bacterin for reasons of safety (believed to be associated with fewer adverse reactions).

The minimum DOI for the recombinant vaccine is at least 1 yr, based on challenge.

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Table 1 (cont'd)
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

Can begin as early as 6 wks of age with boosters every 2- 3 wks with the final dose at 12 wks of age (killed).

Two doses, 2- 4 wks apart (if using killed) (manufacturer)

(Not recommended in adult dogs as neither a need nor benefit has been demonstrated.)

It is recommended that animal shelters not utilize the CCV vaccine in routine vaccination programs due to additional costs incurred and the lack of defined benefit. Experience has shown no additional increase in infectious enteritis among adults or puppies subsequent to discontinuing the CCV vaccine.

Neither the MLV vaccine nor the killed CCV vaccine has been shown to significantly reduce disease caused by a combination of CCV and CPV- 2. Only CPV- 2 vaccines have been shown to protect dogs against challenge when these two viruses are used.

The DOI for the CCV vaccine cannot be determined.

Boosters not necessary in dogs >1 yr of age

Infection in puppies and kittens is often subclinical.

Although giardiasis is the most common intestinal parasite among people in the U. S., the source of human infection is

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Table 1 (cont'd)
AAHA 2003 Canine Vaccination Guidelines and Recommendations*

Because the vaccine does not prevent infection, a minimum DOI based on challenge is not reported.

MLV vaccine: One dose

Upon completion of the intial series, and following a booster at 1 yr, revaccination once every 3 yrs is considered protective.

Vaccine Frequency of Use
All commercially available vaccine products have attendant vaccine protocols as defined by their manufacturers. These generally involve an initial (often puppy) series, followed by recommendations for revaccination (booster) at 1 year of age and annually (or less) thereafter. Regardless of product cho-sen, the current controversy over vaccination protocols cen-ters on the traditional recommendation regarding revaccination schedules for dogs >1 year of age. The cur-rently recommended vaccination schedules (with respect to frequency, not product choice) for dogs <1 year of age have not been questioned. Based on a growing body of informa-tion regarding immunology and product DOI in both animals and humans, the need for annual revaccination has been placed in doubt. Duration of immunity is the critical deter-mining factor, but it defies simple definition, principally, because it is derived from a complex interplay between the host’s immune response (see The Immune System as it Applies to Vaccination section) and the vaccine in question, and it is difficult to measure in an individual animal without direct challenge. Current scientific knowledge demonstrates that DOI varies among vaccines and is influenced by vaccine type (e.g., modified live virus [MLV], killed, or recombi-nant), route of administration, and antigen content and often extends for >1 year. This information is summarized in the following section on specific vaccine recommendations.

Specific Vaccine Recommendations: Core Vaccines
Canine Distemper Virus (CDV): Infection with CDV causes significant morbidity in unprotected animals and is associated with high rates of mortality from respiratory, gastrointestinal, and neurological abnormalities; there is minimal geographic difference in its distribution. Therefore, all puppies should be vaccinated with a CDV vaccine, and boosters should be administered throughout the dog’s life [Table 1].
Dogs with unknown vaccine histories should be considered at risk and vaccinated, and boosters should be administered throughout the dog’s life [Table 1]. Challenge of immunity studies have shown that the mini-mum DOI for MLV-CDV vaccines derived from the Rock-born strain and the Onderstepoort strain are 7 and 5 years, respectively, and for the canarypox-vectored CDV vaccine, it is 1 year (not tested beyond 1 year). The minimum DOI for these same vaccines, using antibody titers at levels that provide sterilizing immunity, are 12 to 15 years for Rock-born and 9 years for Onderstepoort [Table 2]. The canary-pox- vectored CDV vaccine does not provide sterilizing immunity in the majority of puppies receiving the required two doses of this vaccine. The recombinant vaccine does provide excellent immunity—infection occurs, but anamnestic (memory) humoral and CMI responses develop and the challenged dog is protected from disease.
Therefore, following the initial vaccination series, revac-cination every 3 years is considered protective for MLV-CDV vaccines and, due to the lack of information, revaccination every year for recombinant CDV vaccines is considered protective.

Canine Parvovirus (CPV-2): Infection with CPV-2 causes high morbidity and mortality in unprotected dogs primarily from gastrointestinal disease; the organism has worldwide distribution. Therefore, all puppies should be vaccinated with a CPV vaccine, and boosters should be administered throughout the dog’s life [Table 1]. Dogs with unknown vaccine histories should be considered at risk and vacci-nated, and boosters should be administered throughout the dog’s life [Table 1].
Challenge studies have shown that the minimum DOI for MLV-CPV-2 vaccines is 7 years. The minimum DOI for these same vaccines based on serological data for sterilizing immunity is up to 10 years [Table 2].
Therefore, following the initial vaccination series, revac-cination with an MLV-CPV-2 vaccine every 3 years is con-sidered protective. However, if a killed CPV-2 is being used, due to lack of DOI information, annual revaccination is recommended unless it is used as a booster following an initial series with an MLV-CPV-2 vaccine. In this scenario, revaccination every 3 years is considered protective.

Canine Adenovirus-2 (CAV-2): Infection with CAV-2 causes a self-limiting respiratory disease in some infected dogs but produces an immune response that cross-protects against canine adenovirus-1 (CAV-1) infection, the etiology of canine infectious hepatitis, which has worldwide distri-bution. The CAV-1 vaccine has been associated with an unacceptable rate of serious adverse events (e.g., interstitial nephritis, anterior uveitis) and should not be administered; however, CAV-2 vaccines are safer. Therefore, all puppies should be vaccinated with a CAV-2 vaccine, and boosters should be administered throughout the dog’s life [Table 1]. Dogs with unknown vaccine histories should be considered at risk and vaccinated, and boosters should be administered throughout the dog’s life [Table 1].
The minimum DOI for CAV-1 and CAV-2 vaccines, based on challenge immunity for CAV-1, is 7 years. The minimum DOI based on antibody titers is at least 9 years [Table 2].
Therefore, following the initial vaccination series, revac-cination every 3 years is considered protective.

Rabies Virus (RV): Infection with RV causes a fatal neuro-logical disease, and infected dogs are a potential source for human infection, resulting in state and provincial laws man-dating RV vaccination. Therefore, all puppies should be vaccinated with an RV vaccine, and boosters should be administered throughout the dog’s life [Table 1]. Booster revaccination should be administered 12 months following initial vaccine and then as required by local, state, or provincial law. Dogs with unknown vaccine histories should be considered at risk and vaccinated, an initial booster should be administered 12 months later, and boosters should be administered throughout the dog's life [Table 1].

The minimum DOI for killed rabies vaccine based on challenge studies is 3 years; based on antibody titers, it is considered to be up to 7 years [Table 2]....

Table 2
Estimated Minimum Duration of Immunity (DOI) of Select Commercially Available
Canine Vaccine Antigens

Canine Parainfluenza Virus (CPV): Canine parainfluenza virus is one cause of the "kennel cough" syndrome, an infection in susceptible, unprotected dogs causing a mild, self-limiting upper respiratory disease; the agent rarely causes life-threatening disease in otherwise healthy dogs.

Leptospira spp.: Infection with Leptospira spp. can cause clinical disease in some unprotected dogs. The organism can infect both dogs and humans; therefore, infected dogs can serve as a source for human infection (i.e., zoonosis) via contaminated urine. There are multiple Leptospira serovars and minimal cross-protection is induced by indi-vidual serovars, especially those defined to be the etiology of recent leptospirosis outbreaks in specific geographic regions.a,5 Currently available vaccines do not contain all known serovars; therefore, dogs considered to be at risk for infection can be vaccinated, but current products do not provide assurance of protection [Table 1].
Leptospira spp. products include two to four serovars; the efficacies of these products are estimated to be between 50% to 75% and the DOI <1 year for the majority of ani-mals that do develop immunity [Table 2]. Immunity is an ill-defined term for Leptospira spp. products. If immunity is defined as protection from infection or prevention of bacter-ial shedding, then there is little or no enduring immunity. If protection is defined as prevention of clinical signs of dis-ease, then duration of immunity could be >1 year. Thus, DOI for Leptospira spp. becomes a problem of definition as to whether the goal of vaccination is interruption of bacter-ial shedding and public health concerns, or the prevention of clinical disease in the dog. It is generally agreed that immunity, however defined, is serovar specific; thus, if only one serovar is present in the vaccine, any protection, if pro-vided at all, is for that serovar (e.g., Leptospira canicola) and not the many others that can infect the dog.

Bordetella bronchiseptica (B. bronchiseptica): Bordetella bronchiseptica is another cause of the “kennel cough” syn-drome. Infection in some susceptible dogs generally causes a self-limiting, upper respiratory disease and rarely causes life-threatening disease in otherwise healthy animals. Clini-cal disease resolves quickly when treated with appropriate antibiotics. Vaccination does not block infection but appears to lessen clinical disease, and vaccines provide a short DOI (<1 year) [Table 2]. It is also unknown whether current vac-cine strains protect against all field strains. Animals consid-ered to be at risk may benefit from vaccination followed by boosters at intervals in line with their risk of exposure [Table 1].

Borrelia burgdorferi (B. burgdorferi): Infection with B. burgdorferi can cause clinical disease syndromes in some sus-ceptible dogs; most dogs infected are subclinically infected. While the organism infects both humans and dogs, it is not a direct zoonosis but a shared-vector zoonosis. The distribution of the tick vector involved is geographically limited and there-fore the incidence of exposure is similarly geographically lim-ited. Dogs previously exposed to B. burgdorferi do not benefit from vaccination and prevention of exposure to the tick vector is an effective preventive approach. Animals considered to be at risk may benefit from vaccination followed by boosters at intervals in line with their risk of exposure [Table 1]. The minimum DOI for B. burgdorferi vaccines is 1 year [Table 2].

Specific Vaccine Recommendations: Not Recommended Vaccines
Canine Coronavirus (CCV): Infection with CCV causes mild gastrointestinal disease unless concurrent infection with CPV occurs. The virus does not generally cause dis-ease in dogs >6 weeks of age and is not indicated in adult dogs. In at least one study, it was shown that vaccination with CPV protected puppies against challenges with both viruses. The incidence of disease and DOI is not known. Vaccination is not indicated in puppies >6 weeks of age, and vaccination of adult dogs is not indicated [Table 1]. At present, there is no indication that this organism produces a disease of clinical significance; therefore, administration of a CCV vaccine is not recommended.
Similar to CPIV, CCV does not cause clinical disease in experimentally challenged susceptible puppies, even those as young as 4 to 6 weeks of age; thus, challenge studies cannot be done unless pups are given immunosuppressive doses of corticosteroids. Serum antibody titers do not corre-late with protection from CCV infection. Thus, for a virus that has not been shown to cause significant disease, and where serum antibodies don’t correlate with resistance to infection, DOI is impossible to determine [Table 2]. Duration of immunity for CCV is a moot point since a need for the vaccine has not been demonstrated. It has been reported that DOI for CCV is the lifetime of the animal whether vac-cinated or not as a result of natural subclinical infection and age-related resistance. Revaccination with a CCV vaccine in the adult dog cannot be justified, nor has it been shown to have value in preventing disease.

Giardia spp.: Infection with Giardia spp. can be subclinical or can cause small bowel diarrhea. The incidence of disease is generally <10% and approximately 90% of dogs respond to therapy; the disease is usually not life-threatening. There are multiple strains of Giardia, and it is unknown whether the vaccine is of value in more than one heterogeneous iso-late. The vaccine does not prevent infection but may reduce or eliminate shedding of the organism and reduce clinical signs, which are rarely seen except in very young puppies concurrently infected with certain viruses and/or bacteria. The DOI is considered to be 1 year [Table 2]. Vaccination against Giardia spp. is not generally recommended [Table 1].

Discussion and Supporting Literature
The genesis of these canine vaccine guidelines and recom-mendations was to inform practitioners of the current vac-cine controversy, clarify any misunderstandings, and encourage practitioners to recognize that immunization of patients is a medical procedure. In addition, the Task Force members felt it was important to provide practitioners with relevant supporting information. While it is beyond the scope of this report to thoroughly discuss the extensive body of knowledge with respect to vaccinology, certain key concepts and principles are fundamental to the understand-ing and critical evaluation of these guidelines and recom-mendations. What follows is a synopsis of some integral concepts pertaining to immunology, DOI, serological test-ing, vaccine production, adverse event reporting, legal implications of biological use, and potential practice impact and opportunities of adopting these guidelines. Some important vaccination “do’s and don’ts” are summarized in Appendix 2.

The Immune System as it Applies to Vaccination
Understanding the immune system provides a basis for comprehending the nature of vaccine immunity. The fol-lowing summary of the salient principles is further sup-ported by suggested texts with more comprehensive discussions and explanations.6-13
Two major types of immunity prevent or limit infectious diseases: nonspecific (innate) immunity and specific (adap-tive) immunity. In nature, it is innate immunity (including skin, hair, tears, normal microbial flora, and mucus and acidity of the gut) that prevents a majority of pathogens from infecting and/or causing disease in animals. Innate immunity also includes type-1 interferons (IFNs), some cytokines (e.g., interleukin-1 [IL-1], tumor necrosis factor [TNF]), complement components, neutrophils, and natural killer (NK) cells. This first line of defense is already active or immediately activated in response to inherent or elabo-rated chemical substances of the infectious agent. Unfortu-nately, current vaccines only occasionally have a significant beneficial effect on innate immunity; however, immunomodulators (i.e., nonspecific immune stimulants), some new experimental vaccines, and certain drugs are being designed and targeted toward enhancing innate immunity as a nonspecific method for disease prevention.
Adaptive immunity is characterized by specificity and memory and is primarily or exclusively the type of immu-nity stimulated when an animal receives a vaccine. This specific immune system is comprised of:

1. Humoral (antibody) immunity, where differentiated B lymphocytes (plasma cells) produce the four immunoglobulin classes: IgG, IgM, IgA, and IgE; phagocytic cells and effector molecules (e.g., comple-ment) also play an important role.

2. Cell-mediated immunity (CMI) is comprised of T lym-phocytes and their effector molecules, including T helper cells, T regulatory cells, T cytotoxic cells, macrophages, and a number of products of the cells called cytokines (e.g., IFN-ã , IL-2, IL-4, IL-12, TNF).

The Immune Response to Vaccination or Infection
When an animal is vaccinated or infected, the immune response includes differentiation and expansion of clones of antigen-specific T and B cells that serve as effector cells for immediate protection and memory cells that provide long-term immunity. The effector cells themselves are usually short lived, dying in days or weeks after stimulation. Mem-ory cells, on the other hand, survive for years, often for the life of an animal for some vaccines and infections. Memory T and B cells and the antibodies produced by long-lived memory effector B cells cooperate to provide protection from challenge at a later time in life for the vaccinated ani-mals that come in contact with the pathogen. Available information suggests that vaccinal protection from infection and/or disease in the dog is regulated primarily by humoral immunity and secondarily by cell-mediated immunity. This finding is particularly true when vaccination is known to prevent reinfection (sterilizing immunity). This is the ulti-mate form of immunity because disease cannot develop when infection is blocked or infection is significantly lim-ited. Sterilizing immunity occurs after effective vaccination (protection) against certain pathogens such as CDV, infec-tious canine hepatitis, and CPV.
However, when vaccination fails to protect against infec-tion and instead protects against the development of clinical disease (as is the case for parenteral CPIV vaccination), sys-temic and local CMI together with humoral immunity (including local IgA antibodies) all play a critical role in preventing or reducing the severity of disease—not by pre-venting infection but by limiting its effects or keeping the infection localized. A CMI response is generally most effec-tive against intracellular pathogens, while antibodies are usually most effective against toxins or pathogens in the extracellular areas. Whether a CMI or humoral response or both are responsible for controlling or preventing the clinical disease depends on the route of infection and the pathogene-sis (the colonization and replication) of the infectious agent. For instance, prevention of clinical disease by many of the respiratory or gastrointestinal tract pathogens requires gen-eration of mucosal CMI and/or humoral immune responses, with IgA being the most effective antibody class.

Types of Vaccines
Just as the natural immune response depends on the type of antigen and the pathogenesis of the organism, these factors must also be considered in order for a vaccine to induce an appropriate immune response. There are several different types of commercially available canine vaccines. The most common vaccines currently in use are infectious vaccines, including MLV and live vectored vaccines. There are also noninfectious vaccines, including killed whole cell vac-cines, subunit killed vaccines, and recombinant subunit vac-cines. 3,7,11-13
Modified live virus vaccines, consisting of avirulent or attenuated viruses that infect the host, are the most common canine viral vaccines. Such vaccines are highly efficacious, inducing stronger local immune responses than comparable killed products through the induction of serum neutralizing antibodies, local antibodies, and systemic and local CMI responses. The MLV vaccines create an immunity that is similar to immunity after an animal recovers from natural infection. There are also modified live bacterial vaccines consisting of avirulent or attenuated bacteria (e.g., B. bron-chiseptica) and, similar to MLV vaccines, the modified live bacterial vaccines are often more effective than their killed counterparts.
The canarypox viral vectored vaccine for canine distem-per virus has the ability to induce CMI and humoral immu-nity, but the humoral response is not as rapid or robust as the antibody responses engendered by MLV-CDV vaccines. When the canarypox viral vectored vaccine is used in pup-pies, at least two doses are required for immunity; whereas one dose of the MLV-CDV vaccine induces a strong, long-lasting immunity when passively acquired CDV antibody is not present in the puppy (e.g., >12 weeks; see Duration of Immunity section). Recent serological data showed that a third dose of CDV recombinant canarypox viral vectored vaccine induces an anamnestic antibody response equiva-lent to the response achieved with a dose of MLV-CDV, suggesting immunity for the recombinant product will last for >1 year and likely up to 3 years.b,16
Killed canine viral vaccines include vaccines for CPV-2, CCV, and rabies virus. Killed vaccines generally require two doses (rabies is an exception), because the response is slower and the immunity is predominantly but not exclu-sively systemic antibody with CMI limited to T helper type-1 effector cells and little or no IgA antibody on mucosal surfaces. Similarly, the killed bacterial products produce pre-dominantly a systemic antibody response. The killed and subunit products include two to four serovars of Leptospira spp., killed B. burgdorferi (Lyme disease), B. bronchiseptica, and a killed parasite vaccine for Giardia. There is also an OspA Borrelia burgdorferi recombinant subunit vaccine.

Immunological Factors Determining Vaccine Safety
Several characteristics of vaccines are integral to determin-ing product safety and efficacy, including the nature and dose of the antigen, the use of adjuvants, and the number of vaccinal components in any given product. Although increasing the number of components in a vaccine may be more convenient for the practitioner or owner, the likeli-hood for adverse effects may increase. Also, interference can occur among the components. Care must be taken not to administer a product containing too many vaccines simultaneously if adverse events are to be avoided and opti-mal immune responses are sought.
It is often stated that MLV vaccines are the most effica-cious but that killed vaccines are the safest products; how-ever, in light of advances in vaccine technology, this statement should be carefully re-examined.11,13,14 Presumably, killed vaccines are safest because they cannot cause the disease for which the vaccine was designed to prevent; however, killed vaccines are much more likely to cause hypersensitivity reactions (e.g., immune-mediated disease). If they fail to protect because of poor or no CMI or local humoral immunity, or because it takes much longer to pro-vide protection (e.g., the requirement for two doses of killed CPV-2 for protection), then they clearly are not “safer.” Modified live virus vaccines can and do cause dis-ease because attenuation is a balance between maintaining infectivity while eliminating its pathogenicity. Individual response is dependent on the status of the recipient’s immune system. Thus, an attenuated pathogen in a host which is severely immunosuppressed, or genetically more susceptible, may result in the vaccine causing the disease for which it was designed to prevent. For example, an MLV canine distemper vaccine given to black-footed ferrets will induce clinical disease and death.17 Furthermore, in a small percentage (estimated 0.01%) of dogs, the MLV-CDV vac-cine may cause postvaccinal encephalitis.15,18

The Immune System and Frequency of Revaccination
When vaccinating an animal, the age of the animal, the ani-mal’s immune status, and interference by maternal antibod-ies in the development of immunity must be considered. Research has demonstrated that the presence of passively acquired maternal antibodies significantly interferes with the immune response to many canine vaccines including CPV, CDV, CAV-2, and rabies vaccines. Age of the animal is also an important consideration. Puppies <4 months of age may be more susceptible to disease, and they are the main target for core vaccines. Also, very young and possibly very old animals may have a diminished response to vaccination due to age-related suppression of the immune system. Several other illnesses (e.g., neoplasia, immune-mediated disease, endocrine diseases) and their treatments (e.g., chemothera-peutic medications, immunosuppressive drugs) can influ-ence the immune response to vaccines and should be taken into account when vaccinating individual animals.11-13,18,19
When a healthy puppy’s immune system is initially acti-vated by vaccines through antigenic stimulation, a robust humoral and CMI response is expected to develop with con-comitant effector and memory cells. If a pup fails to respond, primarily due to interference by passively acquired maternal antibody, it is necessary to revaccinate at a later time to ensure adequate immunity. Multiple vaccinations with MLV vaccines are required at various ages only to ensure that one dose of the vaccine reaches the puppy’s immune system without interference from passively acquired antibody. Two or more doses of killed vaccines (except rabies) and vectored vaccines are often required to induce an immune response, and both doses should be given at a time when the passively acquired antibody can no longer interfere. Thus, when puppies are first vaccinated at >16 weeks of age (an age when passively acquired antibod-ies generally don’t cause interference), one dose of an MLV vaccine, or two doses of a killed vaccine, are adequate to stimulate an immune response. When MLV vaccines are used to immunize a dog, memory cells develop and likely persist for the life of the animal. Resident memory cells respond rapidly providing an anamnestic immune response at the time of challenge (infection) with the pathogen.
So why revaccinate animals with these products annually when the minimum DOI (memory cells and antibody) is many years, if not a lifetime, for some of the vaccines? Iron-ically, there is no scientific basis for the recommendation to revaccinate dogs annually with many of the current vaccines that provide years of immunity (e.g., CDV, CPV-2, rabies); however, there are other vaccines that often provide <1 year of immunity (e.g., B. bronchiseptica, Leptospira spp.).3,14,15
Vaccinating an animal multiple times at intervals <2 weeks is likely to cause a hypersensitivity reaction in geneti-cally predisposed animals, and a less than robust protective immune response develops.15

Duration of Immunity

Estimating Duration of Immunity and Frequency of Revaccination
It’s believed that the annual revaccination recommendation originated in the late 1950s when MLV-CDV vaccines were first introduced. This recommendation was based in part on the observation that approximately one-third of the dogs vaccinated with a first generation CDV vaccine as part of a limited experimental trial did not have antibody titers con-sidered protective 1 year after vaccination. Therefore, to ensure the canine population had a protective antibody titer, James A. Baker recommended that all dogs should be revaccinated annually as it was not practical nor cost effec-tive to test each animal for antibody.20 At that time, there were very few vaccines (notably CDV and CAV-1), few people were vaccinating their dogs, and the practice of vac-cination for companion animals was not well established or accepted. In 1961, Piercy wrote the following regarding annual administration of the canine distemper vaccine:
“It is felt, therefore, that the usefulness of booster injec-tions in dogs already immune is still open to question and cannot be truly evaluated until considerably more research has been done. The value of revaccinating dogs whose anti-bodies have declined to a low level, however, is not in doubt. Although a serum analysis (antibody titer) is the most scientific way of judging the need for revaccination, in practice the owner would presumably be obliged to pay a fee for the examination and a further fee should revaccina-tion be advised. The alternative, and less expensive way to the owner, is simply to have the animal revaccinated if there is a reason to doubt its immune status and it is likely to be exposed to infection. The practitioner is favorably placed to advise what should be done in light of such local circum-stances as the incidence of canine distemper in his district, the history of the animal concerned, the risk involved in going to shows and kennels and other similar hazards.

Thus, the practice of annual revaccination was accepted as a “principal of vaccination.” Forty years later, we are finally reviewing the recommendation of annual revaccina-tion. This critical review is based on scientific information and the knowledge of vaccines and immunity which have accumulated over that period.

1. Piercy stated: “The usefulness of booster injections in dogs already immune is still open to question and can-not be truly evaluated until considerable more research has been done.” This statement was made with specific reference to the CDV vaccine. We now know that booster injections are of no value in dogs already immune, and immunity from distemper infection and vaccination lasts for a minimum of 7 years based on challenge studies and up to 15 years (a lifetime) based on antibody titer [Table 2].

2. Piercy comments: “The value of revaccinating dogs whose antibodies have declined to a low level, however, is not in doubt.” Indeed, it is in doubt! Dogs with a CDV antibody titer, no matter how low when challenged, may become infected if antibody levels are below titers which provide sterilizing immunity (i.e., resistance to infec-tion), but they will have protection from clinical disease mediated by an anamnestic humoral and CMI response. However, if after vaccination “no antibody” is detected in the dog’s serum, then there is “no doubt,” as sug-gested by Piercy, that revaccination will be of value in boosting the animal’s immune response.

3. Piercy was very perceptive when he stated, “a serum analysis is the most scientific way of judging the need for revaccination.” This is absolutely correct, and anti-body titer is of great scientific value in determining if the dog has sterilizing immunity. Piercy emphasized the importance of antibodies since he didn’t know about CMI; however, antibody is very important for protecting the vaccinated dog from CDV, as well as several other canine viral infections.

4. The economics of the 1960s remains unchanged today. Piercy’s statement that “it would be less expensive to vaccinate than to have the animal bled and an antibody titer performed” remains, for the most part, relevant to today’s practice economics. However, the ethical issue that our profession struggles with today is whether eco-nomics justifies giving an animal a drug (vaccines are biologic drugs) that is not necessarily required. As a minimum, we should allow pet owners to make this choice rather than make it for them.

5. Piercy’s advice on risk assessment analysis and making the decision to vaccinate is an important medical issue and excellent advice that should receive careful attention whenever vaccines are administered. Which vaccines should be given? When and how often do they need to be given? The answers will undoubtedly vary according to which geographic region the dog resides, the lifestyle of the dog, the age and medical history of the dog, as well as the needs and expectations of the owner. Such questions must be asked if the animal is to receive the best medical care.

There are very few published studies on the minimum DOI for canine and feline vaccines and this is compounded by the fact that the criteria for determining DOI cannot be easily agreed on. Some researchers suggest that the only true way to determine DOI is by way of a prospective study that would be comprised of two (one group vaccinated; one group nonvaccinated) relatively large groups of dogs (repre-senting common breeds) housed within a pathogen-free environment; therefore, at the end of the study, the nonvac-cinated group would remain antibody-negative. Both groups would then be challenged with virulent isolates of each of the pathogens for which the vaccines were designed to provide protective immunity. Few minimum DOI studies using this study design have been done, and few, or none, will be done due to the high cost and difficulty of maintain-ing control (i.e., negative) animals. More important, based on current knowledge of immunity resulting from vaccina-tion, studies of this type need not be done.17,18,22-26
There is no indication that the immune system of canine patients functions in any way different from the human immune system. In humans, the epidemiological vigilance associated with vaccination is extremely well-developed and far exceeds similar efforts in animals whether compan-ion or agricultural. This vigilance in humans indicates that immunity induced by vaccination in humans is extremely long lasting and, in most cases, life-long. Current informa-tion (as presented in the section on Task Force Recommen-dations Regarding the Selection and Use of Canine Vaccine Antigens and Table 2) supports the contention that immu-nity to canine vaccines persists for years.
The canine core viral vaccines have been demonstrated by challenge studies to provide a minimum DOI of at least 3 years, and up to 7 years for some vaccine antigens.3,14,15,27-29 When antibody titers considered to provide sterilizing immunity are evaluated, this minimum DOI is even longer [Table 2].3,14,15,18,30
Duration of immunity for bacterial vaccines is considerably different than for viral vaccines. In contrast to viral immunity, bacterial immunity from vacci-nation is generally limited to <1 year, and the efficacy of most of the bacterial products is considerably less than for the viral products and directed at minimizing clinical signs of the disease in question. Protection from reinfection (ster-ilizing immunity) generally does not occur with canine bacterial vaccines.
Antibody titers from bacterial vaccines generally do not correlate directly with sterilizing immunity, and they would be significant only if there was no antibody detected after vaccination.30 This would be a clear indication that the vac-cine failed to stimulate an immune response. Such vaccines should be given again or another product should be used. Bacterial vaccines, especially killed whole organism prod-ucts like certain Leptospira spp. products or B. bronchiseptica given systemically, are much more likely to cause adverse reactions than subunit or live bacterial vaccines or MLV vaccines, especially if given topically. Several killed bacterial products are used as immunomodulators/adjuvants. Thus, their presence in a combination vaccine product may enhance or suppress the immune response or may cause an undesired immune response (e.g., IgE hypersensitivity or a class of antibody that is not protective).3,14

• to determine if there has been an immune response fol-lowing vaccination
• to determine the duration of immunity
• to ensure the vaccine is immunogenic
• to know precisely when to vaccinate the puppy
• to determine whether the animal is a “low or nonrespon-der” to certain vaccines

The important i