Feline vaccine update (Proceedings)

The American Association of Feline Practitioners (AAFP) recently engaged a panel of U.S. and international veterinary practitioners, researchers, and immunologists to update vaccine guidelines previously published in 2000. The report is available in the November 1, 2006 issue of JAVMA and may be accessed at the AAFP website, www.aafponline.org.

Core vaccines

Panleukopenia (FPV): Vaccines for this disease are available as modified live virus (MLV), killed, and topical (MLV intranasal). Most killed products contain adjuvants, while MLV are adjuvant-free. Kittens should be vaccinated started at 8-9 weeks of age (or as early as 6 weeks) and revaccinated every 3-4 weeks until 16 weeks of age. A booster is given 1 year later, then every 3 years or more.

Because maternal antibodies interfere with vaccination responses in kittens, a series of vaccines is necessary for primary immunization. The exact age to start the vaccines (typically 6-8 weeks) isn't as important as ensuring that the last dose is given at 16 weeks or older. A vaccine given 1 year later will boost the immunity if needed and duration of immunity (DOI) has been shown to be at least 7 years.

There is limited evidence for long-term FPV immunity. A challenge study performed 7.5 years after kittens were vaccinated twice (at 8 and 12 weeks) demonstrated protection. Two serologic survey studies looking at antibody (Ab) levels showed protective levels 3-4 years after kitten vaccination. The current brands and types of vaccines are likely to result in similar immune responses. Choice of a particular product may include consideration of adjuvanted vs. adjuvant-free, as the presence of adjuvant has been linked to inflammation or neoplastic transformation.

Adverse effects may include cerebellar hypoplasia if kittens are vaccinated early (less than 4 weeks of age) or if pregnant queens are vaccinated with MLV products, and there is a report of fatal salmonellosis occurring in kittens 1-2 weeks after MLV vaccination (possibly due to transient immunosuppression but not proven). Topical (IN) vaccine eliminates the risk of injection-site reactions but DOI studies have not been reported.

Herpesvirus-1/calicivirus (FHV-1, FCV): These two viruses are common causes of upper respiratory infections, especially in kittens. In addition, FCV infection may cause febrile lameness, oral cavity disease such as stomatitis, and a virulent systemic infection that may be fatal. As with FPV, these vaccines are available as MLV, killed, and topical (MLV IN) and are always found in combination with each other. An appropriate kitten schedule is similar to that listed for FPV – starting at 6-9 weeks and revaccinating every 3-4 weeks until 16 weeks. A 1 year booster is given, then every 3 years or more.

It is well established that neither vaccine is 100% effective in preventing infection, and "sterilizing" immunity is not possible. Vaccinated cats tend to have less severe disease for a shorter period of time compared with unvaccinated cats. The consensus is that FHV-1/FCV efficacy is approximately 75%. Duration of immunity studies are more difficult to perform, as both vaccinates and controls develop clinical signs after challenge. Cats challenged 7.5 years after vaccination as kittens showed a reduction in clinical signs compared with controls but not full protection. Relative efficacy was estimated at 52% for FHV-1 and 63% for FCV. A second challenge study 30-36 months post-vaccination demonstrated relative efficacies of 67% for FHV-1 and 94% for FCV. Serologic surveys have confirmed that Ab persist at least 3 years after vaccination.

A new calici vaccine is available for the virulent systemic strain (CaliciVax, Fort Dodge). It is a killed, adjuvanted product. Studies have not been published to date on the efficacy, but the risk of pet cats contracting this virus appears to be very low. Routine vaccination of all cats is not indicated at this time.

Adverse effects are rare but after MLV vaccination mild upper respiratory disease may be seen. IN vaccines offer rapid protection (2-6 days) in unexposed cats. In rare cases lameness occurs, possibly due to the MLV calici strain. As with FPV, choice of type or brand should take into account adjuvants (found in killed products), the speed of onset desired, and risk:benefit ratio of injectable vs. topical vaccines.

Rabies (RV): As state, local, and/or provincial laws apply, the Guidelines do not govern the frequency of rabies vaccinations. Some are labeled for 1-year DOI while others have 3-or 4-year DOI. In kittens, 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.

All RV vaccines except one are killed and adjuvanted. Chronic inflammation associated with adjuvanted vaccines has been linked to sarcomas. Because the risk of not vaccinating cats for RV is high (violation of legal requirements), other strategies are needed to help reduce the chance for tumor formation. A non-adjuvanted vaccine produced with recombinant technology (PureVax Feline Rabies, Merial) is available. Currently, it is labeled as a one-year product so it must be given annually. However, the lack of post-injection inflammation and reactivity minimizes any risk of vaccine-induced granulomas or neoplasia. Some practitioners question if it is safer to give a non-adjuvanted vaccine every year or an adjuvanted vaccine every 3 years. While prospective research studies have not addressed this specific issue, it would appear more rational to use non-adjuvanted vaccines whenever possible if the goal is to reduce adverse reactions.

Noncore vaccines

Leukemia virus (FeLV): There is ongoing debate as to which cats should receive FeLV vaccines, and if so when and how often. It can be difficult to assess an individual cat's risk of being exposed. Certainly cats that spend time outdoors are more likely to be infected than indoor cats, but lifestyles and confinement can change through a cat's lifetime. Owners may believe they will keep new kittens indoors for life, but circumstances change.

Kittens are much more susceptible to FeLV infection than adults. Cats older than 1 year of age can be exposed but are less likely to become persistently infected. The minimum age that kittens can be vaccinated (according to label recommendations) is 8, 9, or 10 weeks, depending on the brand, so FeLV is typically not given to kittens presented at 6-8 weeks of age.

After two vaccinations 3-4 weeks apart (for either kittens or adults), a booster is given 1 year later. Afterward, annual revaccination is recommended as extended DOI studies have not been performed. A one-year challenge study is available for one vaccine (Leukocell 2, Pfizer). Kittens were vaccinated at approximately 9 and 12 weeks of age and challenged oronasally one year later. 14/18 vaccinates (78%) were protected. However, only 9/15 (60%) of controls (nonvaccinates) became infected, so the preventable fraction was 63%. The likely explanation for the 6/15 young adult cats that were not infected by the challenge is age-related resistance. The 4/18 cats not protected despite vaccination indicates that FeLV does not always induce immunity. A relative lack of efficacy was observed in an outdoor colony where 3 of 5 FIV+ cats became infected with FeLV even after annual vaccination (Leukocell 2). All 19 FIV- cats were protected from FeLV up to 5 years with annual vaccination.

The safety of FeLV vaccines has been a concern ever since the recognition of injection-site (or vaccine-associated) sarcomas. Some studies suggest that both rabies vaccine (RV) and FeLV are associated with an increased risk of post-vaccination chronic inflammation, most likely due to adjuvants. Some practitioners now limit FeLV vaccines to cats at risk of exposure, while others recommend routine vaccination to most or all cats. The current AAFP recommendation is to vaccinate all kittens due to their higher risk of infection and unknown indoor/outdoor status later in life. For adult cats, more selective use is appropriate, considering that inflammation and neoplasia (while rare) can be a significant problem.

Another strategy to minimize the risk of FeLV vaccine-associated sarcomas is to use a nonadjuvanted product. Currently, only one type is available (PureVax Recombinant Leukemia, Merial) that is produced with recombinant technology and delivered transdermally with a needle-free injection device. Studies and clinical experience to date suggest that post-vaccination inflammation does not occur, which suggests that neoplastic transformation is unlikely. This vaccine stimulates both humoral and cell-mediated immunity because of delivery directly to dendritic (antigen-presenting cells) in the skin. This is in contrast with other vaccines that are injected into the subcutaneous space and are not in direct contact with the immune system.

Immunodeficiency virus (FIV): Vaccines to protect against FIV have been difficult to produce due to variation in strains (also called clades) and possible lack of cross-protection. Currently, one type is available (Fel-O-Vax FIV, Fort Dodge) that contains clades A and D. In most areas of the U.S., clade B is the most common field strain. The prelicensing study by the manufacturer indicated a preventable fraction of 82% after a one-year challenge. Subsequent studies using clades A or B as challenge have yielded conflicting results. Space limitations prevent a full discussion of the published research to date.

The vaccine is given at 8 weeks or older with 2 additional doses needed at 2-3 week intervals. The product is a killed, adjuvanted vaccine and recommended for annual revaccination. Reports of FIV vaccine-associated inflammation or neoplasia have not been published, but there is a theoretical risk. The vaccine consistently induces anti-FIV antibody formation, which leads to positive results in all diagnostic tests (ELISA, Western blot, IFA, immunochromatography). PCR assays have been developed to detect FIV but to date have not been successful or accurate in differentiating vaccinated from infected cats. The most susceptible population is outdoor fighting cats. If FIV vaccines are used, cats should first be tested FIV- and then ideally identified as an FIV vaccinate to prevent diagnostic confusion in the future. Microchips, tattoos, or other means of permanent identification have been suggested.

Chlamydophilosis: The syndrome caused by Chlamydophila felis (formerly Chlamydia psittaci var felis) is typically conjunctivitis with or without mild sneezing. As the infection is mild, easily diagnosed, and responds well to treatment, vaccination is considered noncore. Both adjuvanted and nonadjuvanted killed and MLV vaccines are available in combination with other antigens. As with FHV-1 and FCV vaccines, there is no protection against infection. Instead, the severity of disease is lessened in vaccinates but the organism may continue to be shed.

The schedule is the same as the other respiratory vaccines. No duration of immunity studies have been published, so annual revaccination is recommended. Adverse reactions to this vaccine are rare but transient fever, anorexia, lethargy, and lameness have been reported 1-3 weeks post-vaccination.

Bordetellosis: Until recently Bordetella bronchiseptica (Bb) was not considered an important pathogen in cats. Research and field cases have now demonstrated upper respiratory disease in cats infected with Bb. Currently, only one vaccine is available, a topical (IN) MLV product (Protex-Bb, Intervet). The manufacturer recommends one dose for kittens 4 weeks of age or older with no revaccination interval specified. A challenge study demonstrated at least one year duration of immunity. It is difficult to recommend this vaccine for routine use, as respiratory disease caused by Bb is uncommon and is treatable. In shelter situations, anecdotal reports are mixed.

Not generally recommended vaccines

Feline infectious peritonitis (FIP): One vaccine has been marketed to prevent FIP, a disease caused by a mutation of feline enteric coronavirus (FCoV). While exposure to coronavirus is common (approximately 40-50% of household cats and up to 90% in catteries), only a small percentage of cats develop FIP. A genetic predisposition to disease is possible, and kittens are at higher risk than adult cats.

The manufacturer's recommendation (Primucell FIP, Pfizer) is to vaccinate kittens 16 weeks of age or older followed by a booster 3-4 weeks later and annual revaccination. Early studies by the manufacturer indicated good protection against FIP. Subsequent research has indicated no benefit to vaccination in cats already exposed to FCoV (Ab positive). One study of natural exposure found that vaccinated cats were more likely to die of FIP than nonvaccinates (preventable fraction of -20%). If FIP vaccination is considered, kittens or cats should first be tested for anti-FCoV antibodies. If positive, the vaccine will not be protective.

Giardia lamblia: This killed, adjuvanted vaccine may reduce shedding of cysts in infected cats but does not prevent infection. The manufacturer recommends vaccinating kittens 8 weeks or older with a booster 2-4 weeks later, then annual revaccination. A prelicensing challenge study one year after vaccination demonstrated a reduction in diarrhea, cyst shedding, and infection. Another study of young cats followed for 28 weeks showed no difference in cyst shedding between vaccinates and controls, and no reduction in clinical signs (although diarrhea was very mild in both groups). Variations in field strains and the fact that disease is mild or asymptomatic in some cats makes efficacy and DOI studies difficult.

Shelter medicine considerations

Because of crowding, stress, and the high risk of contagious disease, vaccination of all kittens and cats is important. Modified-live products should be used for faster onset of protection. Intranasal vaccines (rhinotracheitis and calici) may be more effective in controlling upper respiratory infections than injectables. Vaccination should occur prior to or immediately upon entrance to the shelter. A delay of even 1 or 2 days may compromise protection. Foster care away from the shelter environment is recommended up to 8 weeks of age.

FPV (MLV injectable), FHV-1, and FCV (MLV, intranasal or injectable) should be started at 4-6 weeks of age and repeated every 2-3 weeks until 16 weeks of age. Even pregnant queens should be vaccinated immediately with FPV killed and FHV-1/FCV MLV rather than waiting. Bordetella vaccines are noncore but may be considered. RV may be given at discharge if kitten is 12 weeks of age or older. FeLV and FIV vaccinations are not generally recommended in shelters.