2009 vaccine update: core vaccines and realistic protocols for dogs (Proceedings)

In recent years, vaccination protocols have undergone a number of changes, such as which vaccines to give, when, and how often. A significant improvement has been the classification of vaccines into categories of core, noncore, and not recommended. While not everyone agrees with which vaccine products belong in which category, there is a general consensus that we can no longer vaccinate every animal with every available vaccine every year. There are far too many individual products, types, and brands to attempt to use them all. Instead, practitioners must choose which vaccines are necessary, which are optional, and which are never used in their clinics. The following guidelines are based on the 2006 AAHA Canine Vaccine Guidelines, which were published in JAAHA and available on the Internet.

Core vaccines

Certain vaccines are recommended for every dog, regardless of region, lifestyle, or other factors. The diseases are not easily treated and are often fatal. Therefore, all dogs should receive these core vaccines as a puppy series (primary immunization) and continued as adults.

Distemper

Widespread vaccination has reduced the incidence of canine distemper to the point where younger practitioners may never have seen a case. However, the virus is still a danger and outbreaks are reported in shelters and in areas where vaccination of the population is inadequate. Two types of distemper vaccine are currently available: modified live virus (MLV) and recombinant (canarypox). Either type can be administered to puppies and adult dogs.

Vaccination should begin at weaning (6-8 weeks of age) and continued every 3 weeks until puppies are 16 weeks of age. Maternal antibody interference can prevent good immune responses to vaccination, so repeated vaccination is necessary. One study suggested that recombinant distemper vaccine overcomes this interference and may be more effective than MLV when rapid immunity is needed, such as during an outbreak.

Practitioners may choose to vaccinate most dogs with most or all of the vaccines available, with the belief that prevention is better than treating the disease. In the 1960s through the early 1980s, this practice was common and quite easy, as the only vaccines available were DHLPP and rabies. Today there are far more vaccine products, new antigens, different combinations, and even different disease patterns than in the past. It is now virtually impossible to vaccinate every dog with every available product. To address this increase in number and complexities of vaccines, the Guidelines categorize them as core, noncore, and not recommended. As the names imply, vaccines that all dogs should receive are core, while noncore are optional based on lifestyle, local disease prevalence, and risk/benefit ratios. The third category of "not recommended" has proven to be controversial, as some vaccines that practitioners use commonly and believe are helpful (and actively marketed by vaccine companies) are now discouraged.

Duration of immunity

Another controversial approach in both the 2003 and 2006 Guidelines is to administer core vaccines every 3 years instead of annually. Veterinarians have questioned both the legality and wisdom of delaying boosters for 3 years when vaccine labels clearly state that annual revaccination is recommended. Discussions of "off-label" use and whether practitioners will be held responsible if something goes wrong are common. There was and is a feeling that annual vaccinations have nearly wiped out common infectious diseases and any change would be a regression, possibly leading to outbreaks. The potential loss in practice income if annual vaccinations were discontinued has been a major concern. The question is asked "Why every 3 years instead of every 2, or 4, or some other interval?" And perhaps the underlying issue is "if it ain't broke, why fix it?".

Research undertaken by several vaccine manufacturers and independent investigators since the 2003 Guidelines were published have demonstrated that core antigens do indeed protect dogs from challenge 3 years after vaccination. Many practitioners were reluctant to consider 3-year intervals because no challenge studies had been published. Now we not only have peer-reviewed research to back up 3-year duration of immunity (DOI) but also a USDA-licensed vaccine.

Serologic testing

The 2006 report expands on the use of blood (serum) testing to determine the immune status of dogs. An in-clinic diagnostic test (TiterChek, Synbiotics) is now available to assess antibody (Ab) titers against canine distemper (CDV) and parvo (CPV). Clinicians are also making use of tests offered at reference labs. While Ab titers are available for many infectious diseases, only CDV, CPV, and rabies are commonly run (and rabies titers are limited to suitability for export). A high titer to either CDV or CPV does demonstrate protection against infection. However, 5-20% of dogs do not have a positive (or adequate) titer. These dogs may be susceptible to infection, but more commonly are fully protected due to the memory capacity of the immune system and cell-mediated immunity. Titers may be run 2 weeks or more after the last vaccination in a puppy series to document seroconversion (appropriate response to the vaccine). If low or negative, another vaccination (preferably with a different brand or type) can be given to stimulate an immune response, and retesting is done 2 weeks later. Titers may be used to document DOI, and several publications have used Ab titers rather than challenge to show protection. Due to variations in lab assays, different reference ranges, and other factors, titers should not be compared between different laboratories.

USDA label requirements

A sticking point for many regarding changes in annual vaccination is the label found on most vaccines that states "annual revaccination is recommended". Is this a legal standard or just a suggestion? Is the 1-year DOI backed by scientific studies or just a guess? Are veterinarians liable or negligent if they give a 1-year vaccine every 3 years (or some other interval)? Or conversely, are veterinarians likely to be sued if they continue to give annual vaccinations despite the Guidelines that recommend every 3 years for some products? These questions are complex, but in a nutshell the USDA Center for Veterinary Biologics (CVB), which licenses and regulates all vaccines and biologics, does not have an "off-label" legal definition as does the FDA (which regulates veterinary drugs). Any licensed veterinarian may use a vaccine with "discretion" as long as it meets the "standard of care" of the profession. The Guidelines and other literature now support longer DOI (such as every 3 years), which complies with the CVB.

Surprisingly, very few vaccines have been subject to 1-year challenge studies despite the 1-year revaccination interval found on most labels. In fact, vaccines are commonly tested in puppies approximately 3 weeks after vaccination. Exceptions are rabies vaccines (usually tested at 1- and 3-years in challenge studies), several newer vaccines, and certain products sold in Europe (as regulations there require studies to support DOI on the label). The CVB is in the process of evaluating some of these label issues, which should benefit the profession.

A positive development that arose after the 2003 Guidelines is that most vaccine manufacturers now fully support veterinarians who use their products in extended DOI protocols. If any questions or problems arise, the companies will stand behind the efficacy of their products. In some cases, companies have offered specific warranties when certain vaccines are used every 3 years. Also, the AVMA insurance trust has agreed that in following these and similar Guidelines, all insured veterinarians will receive full legal support if any claims of negligence arise.

Individual vaccine guidelines

The rest of the discussion will focus on specific diseases and available vaccines. Reasons for categorizing and evidence for the proper use of canine vaccines will be reviewed.

Canine distemper (CDV) - core

For both modified-live (MLV) and recombinant (rCDV) vaccines, a puppy series should be started at 6-8 weeks of age, then every 3-4 weeks until 12-14 weeks of age. A booster is given at 1 year, then every 3 years or more is considered protective.

This schedule for puppies has been long established and is not controversial. Vaccinating every 2 weeks is unlikely to stimulate immunity any better or faster and may even interfere with appropriate responses. The main issue is whether adult dogs over 1 year of age should be vaccinated annually (as has been done since the 1950s and is recommended on most labels) or triennially. Evidence has been accumulating that every 3 years or even longer is fully protective.

A controlled research study looked at 22 Beagles vaccinated with a new type of MLV vaccine (Continuum DAP, Intervet) at 7 and 11 weeks of age found that all survived an intracranial CDV challenge administered 39 months after the vaccines. The results of this study supported the USDA-approved label claim of protection up to 3 years after initial and booster vaccination.

Another controlled study of a new MLV vaccine (Duramune Adult, Fort Dodge) also used puppies vaccinated at 6-8 weeks of age and again 3 weeks later. The 10 vaccinates were similarly challenged 3 years later and all survived. This product has an approved label stating it is well suited as a booster vaccination for adult dogs when following an extended vaccination interval program.

In a third study of 10 Beagle puppies, a traditional (rather than new formulation) MLV CDV (Galaxy, Schering-Plough) was given at 7-8 weeks of age and again 3 weeks later. An intranasal and intravenous (not intracranial) challenge was performed 57 months later (close to 5 years) and all vaccinates except one were fully protected. The nonprotected dog had clinical signs of distemper but recovered after 14 days. This dog was a nonresponder (did not develop a positive Ab titer after vaccination). Therefore, the overall protection rate was 90%.

A fourth study was a serologic survey and looked at Ab levels in client-owned dogs. As this was not a controlled research study in a laboratory (like the others), the results are more open to interpretation. Of 322 dogs vaccinated with a traditional product (Vanguard Plus 5/L, Pfizer), 316 (98%) maintained a protective Ab titer for up to 48 months. Because these were pets, they were not challenged to test actual protection but other studies have demonstrated that positive Ab titers are sufficient to protect dogs if exposed to CDV.

An unpublished study using rCDV demonstrated protection from intranasal challenge in dogs 2.5 years after primary vaccination. These results have led to a change in the 2006 Guidelines, as the 2003 version recommended annual boosters if rCDV is used. Now, rCDV along with MLV products are both suitable for use in 3-year protocols.

The conclusion from these and other unpublished studies is that in the vast majority of dogs, immunity after primary vaccination as puppies persists for at least 3 years and potentially longer. There is currently no way to test for "maximum" DOI, so it is unknown if dogs are protected for extended intervals such as 10 years. One investigator has estimated minimum DOI of ≥5-7 years after MLV vaccination and ≥3 years after rCDV. The additional vaccine recommended at 1 year of age (or 1 year after the final puppy vaccination) is extra "insurance" of long-term protection but was not included in the challenge studies.

Canine adenovirus type 2 (CAV-2) – core

For MLV (parenteral) vaccines, a puppy series should be started at 6-8 weeks of age, then every 3-4 weeks until 12-14 weeks of age. A booster is given at 1 year, then every 3 years or more is considered protective. Topical (intranasal) CAV-2 is available in combination with Bordetella and parainfluenza, but is "not recommended" in this form due to a poorer immune response.

As with CDV, there is no controversy over the puppy schedule. The disease induced by CAV-1, infectious canine hepatitis, is rare and many practitioners have never diagnosed a case. Because the virus is still found in wildlife, dogs may be exposed and so the vaccine remains a core product.

DOI studies for CAV-2 were included in the above CDV descriptions. 23 dogs challenged with IV CAV-1 37 months post-vaccination (Continuum DAP) were all protected. In study 2, all 14 puppies were protected after IV challenge 36 months post-vaccination (Duramune Adult). The third study of 10 dogs challenged 56 months post-vaccination (Galaxy DA2PPvL+Cv) also showed 100% protection. The serologic study of Ab titers demonstrated adequate protection for up to 48 months after vaccination (Vanguard Plus 5/L).

Canine parvovirus (CPV-2) – core

For MLV vaccines, a puppy series should be started at 6-8 weeks of age, then every 3-4 weeks until 12-14 weeks of age. A booster is given at 1 year, then every 3 years or more is considered protective. Killed parvo vaccines are "not recommended" because of increased maternal Ab interference and the need for multiple doses up to 18 weeks of age or older.

As parvo is commonly seen by most practitioners, with high morbidity and mortality in unvaccinated or improperly vaccinated puppies, there is some reluctance to alter protocols to extended intervals. In fact, some veterinarians recommend vaccinating every six months for parvo. However, improved vaccines developed in the 1990s have overcome the common problem of persistent maternal Ab interference, and clinical experience confirms that CPV may be given at the same schedule as CDV and CAV-2. All CPV-2 vaccines protect against all field isolates (CPV-2, CPV-2a, CPV-2b).

The studies noted above for CDV and CAV also included a CPV challenge. Briefly, in study 1 all 22 vaccinates (Continuum DAP) were protected 38 months later. In study 2, all 10 dogs were protected 36 months after vaccination (Duramune Adult). In study 3, 10 dogs were all protected 55 months post-vaccination (Galaxy DA2PPvL+CV). Study 4 also confirmed positive Ab titers up to 48 months after vaccination (Vanguard Plus 5/L).

The consistent findings in these studies that puppies vaccinated twice and challenged 3 to 5 years later remained protected should reassure veterinarians that the 2006 Guidelines are accurate, reasonable, and backed by research. The additional vaccines recommended by the Guidelines at 12-14 weeks and at 1 year provide a layer of extra protection if, for whatever reason, puppies do not fully respond to their two primary vaccinations.

Canine parainfluenza virus (CPIV) – noncore

The 2006 Guidelines have changed CPIV from "recommended" to "noncore", presumably because the disease caused by the virus (usually a self-limiting cough) is mild rather than fatal as with the core viruses. The parenteral (injectable) MLV vaccines are given to puppies at the same schedule as CDV, CAV-2, and CPV as they are only sold in combination. Topical (intranasal) MLV vaccines are marketed in combination with Bordetella with or without CAV-2. Very few studies have been performed on CPIV infection or the protection offered by vaccines. Unpublished research has shown a minimum 1-year DOI for topical CPIV. Because of the lack of peer-reviewed studies of CPIV, the Guidelines should be seen as expert opinion and personal experience. Dogs at risk of exposure should ideally be vaccinated with IN products at least one week beforehand. A 3-year revaccination interval is recommended after a puppy series and a 1-year booster.