Canine vaccine update (Proceedings)

After the publication of the 2003 AAHA Canine Vaccine Guidelines (JAAHA, Mar/Apr 2003, vol. 39), much discussion and controversy arose among practitioners, industry, and even the general public. Some practices adopted the Guidelines as written while others only incorporated certain portions. A number of veterinarians were not aware of the recommendations. Also, some individual and group practices took a look at the Guidelines and decided not to implement any of them. In 2005, the Task Force reconvened to update the Guidelines, and the results were published in the Mar/Apr 2006 issues of JAAHA and Trends. The document is also available at the AAHA website, http://www.aahanet.org

As veterinary practices evaluate current protocols and decide if any changes are worthwhile, it's helpful to review evidence from published scientific literature. Marketing materials from vaccine manufacturers may be helpful in knowing what's available, but advertising claims may not match the evidence. The following update on canine vaccines is designed to help sift through recent publications and help veterinarians formulate a reasonable vaccination protocol.

Classification of vaccines

Practitioners may choose to vaccinate 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 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 complexity, the Guidelines categorize vaccines 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.

Core vaccines

Distemper (CDV): 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 14-16 weeks of age. A booster is given at 1 year, then every 3 years or more is considered protective. Distemper outbreaks occur from time to time in the U.S., and the virus is maintained both in canine and wildlife populations. Because the disease is highly contagious and causes significant morbidity and mortality, vaccination of all puppies and dogs is important.

A controlled research study looked at 22 Beagles vaccinated with a MLV vaccine (Continuum DAP, Intervet) at 7 and 11 weeks of age and 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 MLV vaccine (Duramune Adult, Fort Dodge) 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, an existing rather than new MLV vaccine (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. Of 322 dogs vaccinated with an existing 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 but other studies have demonstrated that positive Ab titers are sufficient for CDV protection.

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.

Adenovirus type 2 (CAV-2): For MLV (parenteral) vaccines, a puppy series should be started at 6-8 weeks of age, then every 3-4 weeks until 14-16 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. 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).

Parvovirus (CPV-2): For MLV vaccines, a puppy series should be started at 6-8 weeks of age, then every 3-4 weeks until 14-16 weeks of age. A booster is given at 1 year, then every 3 years or more is considered protective. 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 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).

Rabies: As state, local, and/or provincial laws apply, the Guidelines do not govern the frequency of rabies vaccinations. All available products are killed vaccines, and some are labeled for 1-year DOI while others have 3-year DOI. In puppies, one dose is given at 3 months of age or older, followed by a second dose 1 year later. After these vaccinations, boosters are given every 1 to 3 years depending on legal requirements. A 3-year vaccine may be substituted for a 1-year vaccine but the reverse is not true (a 1-year labeled product cannot be used instead of a 3-year). Despite the fact that some brands of rabies vaccine are identical whether labeled as 1- or 3-year, careful adherence to local laws is necessary.

Noncore vaccines

Parainfluenza virus (CPIV): The 2006 Guidelines changed CPIV from "recommended" to "noncore", presumably because the disease caused by the virus (usually a self-limiting cough) is mild. 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. 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.

Bordetella bronchiseptica (Bb): This vaccine is available as a live avirulent bacterin for topical (intranasal) use or as a parenteral (injectable SC) cell wall antigen extract. Bb causes infectious tracheobronchitis ("kennel cough") which is often mild and self-limiting but occasionally can lead to pneumonia or other severe complications. As a noncore vaccine, dogs at risk of exposure should be vaccinated.

The topical products should be given as a single dose according to label instructions (as early as 3 weeks of age depending on type). A second dose can be given 2-4 weeks later for best results. Annual revaccination is recommended or even more often in high-risk animals. A booster is suggested 1 week before exposure if more than 6 months has elapsed since the last Bb vaccine. Duration of immunity is thought to be at least six months but in some cases much longer. There are no studies suggesting extended intervals such as every 3 years. Transient coughing, sneezing, or nasal discharge is occasionally seen as a post-vaccination adverse reaction.

Injectable Bb vaccine is recommended for puppies at 8 and 12 weeks of age followed by annual revaccination. In high-risk environments, every 6 months is suggested as a booster interval. As with IN vaccines, a booster is helpful given 1 week before exposure.

There is no benefit in vaccination with both IN and SC on the same day. However, giving both products in sequence every 2 weeks was shown in one study to provide excellent protection. Two groups of puppies were vaccinated every 2 weeks starting at either 14 or 16 weeks of age and given an IN followed by two SC or two SC followed by an IN. Another two groups received either one IN or two SC but not both. The results showed that puppies in the first two groups (either receiving IN, SC, SC or SC, SC, IN every 2 weeks) had fewer clinical signs after challenge at 20 weeks of age than puppies receiving one product or the other.

Leptospirosis: This disease does not appear to be a threat in all areas. The risk of dogs' contracting lepto is assumed to be from exposure to wildlife or even urban pests such as squirrels or rats. Rainfall and moist conditions appear to increase the incidence. Many more dogs are exposed than become clinically ill, and asymptomatic dogs may shed lepto spirochetes in the urine. For at-risk puppies and dogs, one vaccination at 12 weeks followed by a second at 14-16 weeks is recommended. Annual boosters, or even at 6-9 month intervals for high exposure situations, are then continued. There is currently no evidence of long DOI. In a study of a bivalent (L. interrogans serovars canicola and icterohaemorrhagiae) vaccine (Novibac Lepto, Intervet), puppies were protected 56 weeks after vaccination at 9 and 13 weeks of age.

Currently, two products include additional serovars (pomona and grippotyphosa) (Duramune 4/L, Fort Dodge and 4L, Pfizer). Recent studies suggest that these two serovars are responsible for most of the clinical disease diagnosed rather than the original serovars found in all lepto vaccines. However, because of cross-reactivity in diagnostic assays, the exact serovar causing an infection is speculative (based on high Ab titer responses) rather than proven.

Practitioners often ask if leptospirosis is a problem in their practice area and whether routine vaccination is worthwhile. The risk:benefit ratio is a little different for lepto vaccines than for other products, as acute anaphylaxis in puppies, toy breeds and small dogs is more common. Because there is no central reporting database for veterinarians to refer to, questions about prevalence in an area should be directed to diagnostic labs at nearby veterinary schools or state facilities. If practices with large caseloads are seeing clinical leptospirosis, or if labs in the area are diagnosing positives, then vaccination is recommended. Otherwise, lepto may be safely omitted from routine protocols. No vaccine is 100% protective and there is a potential for infection by other serovars not covered in the vaccines (such as bratislava and autumnalis).

Lyme disease (Borrelia burgdorferi, borreliosis): Two types of vaccines are currently available – killed whole cell bacterins and recombinant-outer surface protein A (rLyme or OspA) products. Lyme disease is considered endemic in parts of the Northeast and upper Midwest, and also occurs in the far West and eastern seaboard. Some areas of the country are free of Lyme disease unless humans or animals have traveled to other areas. The noncore status is likely due to this geographic limitation along with the fact that Lyme disease is nonfatal and treatable (with the possible exception of Lyme nephritis, an emerging complication).

Puppies at risk are vaccinated at 9 to 12 weeks of age followed by a second dose 2-4 weeks later (manufacturer recommendations should be followed). Annual revaccination, preferably just before tick season, is recommended. Extended DOI are not appropriate. Only a minimum 1 year protection from challenge has been shown.

There is much debate over the usefulness of Lyme disease vaccines, especially in seropositive dogs (those that have a positive Ab titer to Borrelia due to previous exposure). In endemic areas, the majority of dogs are seropositive but asymptomatic. Some experts recommend avoiding Lyme vaccine in any dog testing positive for Ab. Other experts feel it may help both with current disease and as protection against future infections. Further research is needed to clarify this issue. There is a consensus that tick control is at least as important as vaccination in Lyme-endemic areas.

Vaccines not recommended

Coronavirus (CCV): In both the 2003 and 2006 Guidelines, CCV is not recommended for any puppies or adult dogs. This is in contrast to the popularity of CCV vaccines, as sales statistics indicate that more than 50% of combination vaccines include CCV in addition to CDV, CPV, etc. CCV is also sold as a single antigen product. The reason for the widespread use of this vaccine despite little evidence of its usefulness or efficacy is the result of advertising and marketing.

The Task Force has determined that clinical CCV disease occurs rarely and is mild and self-limiting. Neither MLV nor killed vaccines have been shown to reduce disease caused by CCV and CPV-2. Also, efficacy and DOI cannot be accurately determined as studies performed to date have failed to show evidence of disease in either vaccinates or control dogs. Veterinarians who have discontinued CCV vaccination in their practices have not reported an increase in infectious enteritis. Extensive literature searches have failed to find research studies or publications supportive of CCV as a serious illness or the need to vaccinate.

Giardia lamblia : This killed vaccine may reduce shedding of cysts in infected dogs but does not prevent infection. Therefore, the 2003 and 2006 Guidelines do not recommend its use in any dog. Because there is no protection against infection, there is no duration of immunity reported.