Vaccine Recommendations: The Good, the Bad and the Ugly

Dennis W. Macy DVM, MS

Colorado State University, Fort Collins, Colorado 80523

Recommendations for immunization of cats should reflect current disease risk, understanding of currently available vaccines, scientific information on immunity and disease pathogenesis, and should not necessarily be based on traditions, customs and practices used 30 years ago. As responsible health care professionals, we must be able to critically evaluate our current immunization practices and be able to ask the same hard questions of both old and new vaccination protocols in order to pass unbiased medical

judgment in determining what is medically correct for our feline patients. Finally, we must separate monetary motives when looking at the medical need for annual vaccination of cats.

The current practice in preventive veterinary medicine, which has been "if it is available, give it and give it yearly" is changing. Not all cats need all available vaccines nor do they need any of them annually. Rabies, Microsporum canis, panleukopenia (FPV), feline viral rhinotracheitis (FHV-1), calicivirus (FCV), FeLV, feline infectious peritonitis, Chlamydia psittaci, Bordetella bronchiseptica,, and Giardia vaccines are available for cats. With the exception of some rabies vaccines, all feline vaccines are recommended by the manufacturer to be given annually. Are all these vaccines really necessary for every cat every year? Are there published case reports of clinical disease in vaccinated cats that miss their boosters? Do you receive all available human vaccines yearly? What is the scientific evidence that the feline immune system is that much different than that of humans? The American Association of Feline Practitioners, at least ten North American Colleges of Veterinary Medicine, the American College of Veterinary Internal Medicine (oncology specialty), the United States Army veterinary hospitals worldwide, and veterinary virologists now endorse similar recommendations of a limited number of vaccines.^43-46 Core vaccines, those that should be administered to all cats, include FPV, FHV-1, FCV and rabies virus. Following the initial vaccination period and 1 year booster, these vaccines should be administered no more frequently than every three years. Vaccines considered non-core are those to be used only in some cats or special circumstances. Examples include vaccines for B. bronchiseptica, feline infectious peritonitis, feline leukemia, C. psittaci, Giardia, and M. canis.

To understand the criteria for vaccine selection and booster frequency recommendations, I believe we must look at the basis of current annual vaccine labeling. ⁴⁷ Other than rabies, no minimum duration of immunity data is required for veterinary vaccine licensure. Until recently, a manufacturer of United States veterinary vaccines could merely show protection two to four weeks after the initial vaccine series. Since the booster recommendation is not required to be based on scientific data it is considered arbitrary! Manufacturers do not even have to show a rise in titer levels after boostering, let alone enhanced protection by challenge with annual booster vaccination. This is not the case in Europe where minimum duration of immunity data based on challenge data must be submitted prior to veterinary vaccine licensure. Even with rabies vaccines, the vaccine label is not always representative of the true product. For example, a rabies vaccine that meets challenge requirements for a three year duration of immunity may be simply relabeled as a one year vaccine under current USDA regulations. Thus a conscientious veterinarian who wanted to use a true one year vaccine with less adjuvant and less vaccine site inflammation may be really using a three year vaccine legally relabeled as a one year vaccine. The USDA does not even require a warning label for anaphylaxis or injection site sarcoma development despite the multiple published reports documenting these adverse events.

Since the majority of manufacturer label recommendations were arbitrarily determined, conscientious veterinarians are forced to use other criteria to establish frequency of revaccination of cats. Epidemiologic information can be very beneficial. For example, feline panleukopenia is not diagnosed in the same cat twice or in cats that have ever been vaccinated suggesting the duration of immunity following natural infection or vaccination is permanent for this agent.

Serum antibody titers are an indirect measure of protection that can be used for some diseases to determine duration of immunity.^48,49 However, there are many limitations. For example, immunity and serum antibody responses may vary with the type of vaccine used (MLV or killed). Additionally, protection against some agents may not be antibody dependent; serum antibody titers do not necessarily reflect cellular or mucosal immunity (feline infectious peritonitis is a good example).⁴⁸ Serum antibody tests are not all the same; technique variation and variation between laboratories may influence interpretation of results. Finally, failure to detect antibodies against an infectious agent in a vaccinated animal does not necessarily equate to susceptibility and should not be used as the sole basis for revaccination (rabies and rhinotracheitis are good examples).⁴⁸

Duration of immunity studies as determined by challenge data appear the most believable, and unlike physicians, "we as veterinarians have the privilege of performing challenge trials." Unfortunately, challenge studies are somewhat expensive, but are not cost prohibitive, as some vaccine manufacturers would like you to believe. The paucity of case reports of disease in previously vaccinated animals, regardless of time since last vaccinated, suggests the duration of immunity is longer than suggested by the manufacturer’s label. Long-term challenge studies have been done for a small group of feline vaccines; results are discussed with each antigen that follows. Each infectious agent is unique and so the mechanism of protection may be different. In general, those agents that produce severe systemic illness like panleukopenia result in life-long immunity after recovery. Those agents that produce superficial infections like rhinotracheitis produce only transient immunity to infection following recovery or the development of a carrier state. In general, MLV vaccines will mimic natural disease protection so those vaccines for systemic diseases like panleukopenia will produce lasting protection while those for superficial infection do not prevent infection but may reduce clinical signs associated with the infection.

Panleukopenia: Panleukopenia is caused by a parvovirus that persists through the environment. In order to prevent cat-to-cat transmission, 98% of the population must be immunized.⁵⁰ This polysystemic infection is potentially deadly to the nonimmunized (especially the young), but recovery from natural infection provides life-long immunity. To my knowledge, reports of clinical panleukopenia in vaccinated cats are lacking. Serum neutralizing antibodies were detected in serum of all 8 cats vaccinated with an inactivated FPLV vaccine held in isolation for six years.⁵¹ Cats vaccinated for FPV have been challenged with virulent virus at 25 months and 7.5 years; 100% of the cats were protected.^52,53 Both modified live virus vaccine and killed vaccines provide good antibody responses. Young kittens with maternally derived FPV antibodies are resistant to challenge with virulent virus documenting FPV serum antibodies to be protective. Since systemic humoral immune responses play a large role in protection against FPV, there is no advantage to intranasal vaccine administration.

Based on the results of these studies, annual revaccination recommendations for panleukopenia appear unnecessary. It seems prudent to follow the three year interval recommendation for this organism.⁴³ However, it is doubtful that revaccination with MLV FPV vaccines after the initial series increases protection against clinical disease and so the revaccination interval could probably be longer. Kittens should be vaccinated with MLV or inactivated FPV every 3 to 4 weeks until 12 weeks of age and then revaccinated 1 year later. After that time, the revaccination interval should be no more than every 3 years.Feline herpesvirus 1. Feline herpesvirus 1 (viral rhinotracheitis) is the most common cause of upper respiratory disease, conjunctivitis, and keratitis in cats.⁵⁰ In general, FHV-1 results in local tissue inflammation and seldomly results in systemic disease or changes in the hemogram. Naïve kittens occasionally develop lower airway inflammation and can be life-threatened. Natural FHV-1 infection results in transient and incomplete immunity in the cat. Mucosal, secretory IgA and cell-mediated immune responses are most prominent in protecting cats against FHV-1. Infected cats may recover from clinical disease, but may remain persistently infected and intermittently shed the virus following periods of stress. Most previously infected or vaccinated cats are protected from developing severe systemic disease if reexposed but can be infected and shed the virus.⁵⁴ Given these characteristics of the immunity derived from natural infections, any vaccine will likely only provide short term local immunity, but are likely to provide adequate stimulation of memory cells to prevent deep invasion of tissues and severe systemic illness.⁵⁴ Vaccinating cats previously infected with FHV-1 probably adds little additional protection to cats. Several studies have shown FHV-1 SN titers to be persistent after use of inactivated FHV-1 vaccines.^51,55 In the longest study, 4 of 8 vaccinated with inactivated FVR vaccine and held in isolation had detectable FHV-1 antibody titers 6 years later.⁵¹ When these cats were challenged with virulent FHV-1 7.5 years after vaccination, clinical scores were 52% less than unvaccinated control cats.⁵³ Similar studies have not been published for the newer modified live virus vaccines. Modified live virus vaccines stimulate a more lasting mucosal immunity, cell-mediated immunity, and humoral response than killed vaccines, thus would be expected to provide even better protection than inactivated vaccines. Recent studies indicate intranasal vaccines are superior to subcutaneously administered vaccines in reducing clinical disease following exposure but have a greater incidence in local side effects. Kittens should be vaccinated every 3 to 4 weeks until 12 weeks of age and then revaccinated 1 year later. After that time, FHV-1 vaccines should not be administered any more frequently that every 3 years.

Calicivirus. FCV induces upper respiratory disease and stomatitis in infected cats. Disease can be severe, particularly in naïve kittens. Following natural infection with feline calicivirus, immunity to reinfection is believed short, but protection against severe systemic illness is sustained.^50,54 Cats recovering from calicivirus induced disease remain persistently infected and continuously shed the virus for months to years. Challenge studies in young kittens with maternally derived FCV antibodies and in immune-vaccinated cats, suggests that FVC serum neutralizing titers greater than 1:16 are protective against disease following a virulent challenge.^56,57 The role of cell-mediated or mucosal immunity in protection against disease has not been established but both are likely to be important. Following administration of inactivated FCV vaccine, SN titers indicating protection were detected in 8 of 13 cats 5 years later.⁵⁸ In a study of cats administered inactivated FCV vaccine and then challenged with virulent FCV 7.5 years later, clinical scores were 63% less than those of unvaccinated control cats.⁵³ Modified live FCV vaccines used today are likely to perform even better than the inactivated vaccine used in these studies. Since mucosal immune responses are likely important, intranasal vaccination is likely to induce more rapid protection than subcutaneous vaccination but is likely to induce more local side-effects. Use of intranasal vaccines in combination with subcutaneous vaccines may provide better protection in the short term, combination protocols are unlikely to provide significantly better protection in the long-term.⁵⁹ Kittens should be vaccinated every 3 to 4 weeks until 12 weeks of age and then revaccinated 1 year later. After that time, FCV vaccines should not be administered any more frequently than every 3 years.Chlamydia psittaci. Chlamydia psittaci infection can be subclinical or results in a moderate to severe conjunctivitis. Environmental conditions and poor husbandry practices appear to enhance the likelihood of clinical illness. The duration of immunity following natural infection is unknown but likely to be short. There is no correlation between circulating antibody titers and protection, and protection is likely to be primarily associated with secretory IgA mucosal immunity or cell-mediated immunity.⁶⁰ Two studies have shown significant but incomplete protection at 12 months following vaccination with an inactivated vaccine.^61,62 Chlamydia vaccines do not prevent infection or eliminate shedding, but do reduce clinical signs. Since the disease is not life-threatening, is uncommon, and is easily treated with inexpensive antibiotics this vaccine is considered non-core and should only be used in catteries with a history of chlamydial disease. Veterinarians should address husbandry practices first in all cases. How frequently the vaccine should be administered is unknown. Like the other upper respiratory vaccines in cats, protection is not complete, and reduction in severity of clinical signs should be our expectation. It is likely that long-term reduction in clinical signs following exposure is associated with the presence of memory cells. Annual vaccination is probably not necessary except in catteries with sustained Chlamydia infections. Bordetella bronchiseptica. This organism is commonly detected in the airways of cats in crowded environments.^63,64 Additionally, many cats are seropositive proving exposure to B. bronchiseptica. However, most exposed cats are healthy with significant clinical illness almost never occurs in adult cats. Occasionally, the organism has been associated with pneumonia in young kittens in stressful environments with poor sanitation. Only one vaccine is currently available; a modified live intranasal product. Immunity is likely mediated by secretory IgA, thus is likely to be short lived as in dogs. Side-effects associated with vaccination are similar to those of the natural infection and occur in at least 2% of vaccinated cats. Since clinical disease associated with B. bronchiseptica is mild to non-existent in pet cats, since vaccine side-effects are similar to natural infection, and since clinically affected cats respond to inexpensive antibiotics, this vaccine is considered non-core. It should only be administered to cats in humane shelters or catteries where documented loss due to Bordetella pneumonia has occurred. If used, vaccination should be used in conjunction with improved environmental and sanitary practices. It should be given intranasally to young kittens only.Feline leukemia virus. This virus induces a multitude of clinical syndromes in infected cats, many of which are life-threatening. The immunity following natural infection is incomplete and some recovered cats can be reinfected with the same strain of FeLV within three years. It is known that protection against natural infection is age related and that 85% of cats under 12 weeks of age if exposed become persistently infected, while cats over six months of age only have a 10%-15% chance of becoming persistently infected if exposed.⁶⁵ Since the most susceptible population is the young, vaccination should be targeted at this group. Since only 10%-15% of adult cats receive any true vaccine protection beyond age acquired immunity and since FeLV vaccines are commonly associated with injection site sarcomas, the risk and benefits of vaccination needs to be presented to cat owners. Duration of immunity studies are limited and have shown great variation between FeLV vaccine manufacturers. Some FeLV vaccines have demonstrated protection to three years, while others have shown no vaccine related protection just 15 months following vaccine administration.⁶⁶ Since antibody titers have failed to reliably correlate with FeLV vaccine protection, they should not be used in evaluating the need for revaccination of cats for FeLV.^67,68 My research suggests the most efficacious FeLV vaccines are the most locally reactive and possibly most likely to be associated with injection site sarcoma development. These vaccines should be considered to noncore and should be administered only to kittens with risk of exposure. Kittens should receive the initial vaccine series and be revaccinated 1 year later. Additional boosters should not be given more frequently than every 3 years until more definite data on duration of immunity becomes available or safer vaccines are developed.Feline infectious peritonitis. Feline infection peritonitis is caused by a feline coronavirus and results in fatal disease in about 1:5,000 average client households. The duration of immunity following natural infections with feline enteric coronavirus (FECV) or the pathogenic variant (FIPV) is unknown. There is no correlation between circulating antibody titers and protection. Both secretory IgA and cell-mediated immunity are thought to provide the greatest protection against infection and clinical disease. Although cell-mediated immunity is likely to be lasting, secretory IgA protection is likely to be short lived (one month).⁶⁹ However, challenge studies have demonstrated some protection in cats 6 and 12 months following vaccination, which is likely to be cell mediated.^70,71 Studies have indicated cats must be coronavirus negative at the time of vaccination and have a serum antibody titer less than 1:100 to receive benefit from the FIP vaccine; at least 20% to 40% of the cat population has antibody titers of this magnitude. The vaccine has a 60-80% preventive fraction at its peak protection time two weeks following vaccination. These findings combined with the relatively rare incidence of disease limits the use of this vaccine to high risk catteries that are coronavirus negative. It is the author’s opinion that a greater decrease in mortality to FIP may be obtained through changes in husbandry practices, such as increasing the number of litter boxes and reducing crowding, than routine FIP vaccination.Microsporum canis. This organism induces skin disease that is not life-threatening and relatively uncommon in the cat population at large. The currently available vaccine is inactivated oil adjuvanted, which produces significant local reactions at injection sites. This non-core vaccine is best reserved for treatment of the clinical syndrome rather than prevention. If ringworm vaccines were used more extensively, they would probably be linked to vaccine site tumor development. Giardia spp. Infection of cats with Giardia induces small bowel diarrhea that is often self-limited or responsive to a variety of anti-protozoal drugs. Incidence varies by region, but was shown to 2.4% in one study in a presumed endemic area (north-central Colorado).⁷² Administration of an inactivated, subcutaneous product resulting in lessening of clinical signs and cysts shedding in vaccinates when compared to controls following heterogenous challenge 1 year after vaccination. Since the product is adjuvanted, there is potential for association with vaccine-associated sarcomas. Based on incidence, availability of effective treatments, and unknown safety issues, the Giardia vaccine is considered non-core and should be reserved for high risk cats or the treatment of chronic carrier cats.Rabies vaccines. Rabies vaccines are the only veterinary vaccine that requires minimum duration of immunity studies prior to licensure. It should be remembered that these vaccines are tested in young, not fully developed animals and that they still must protect at least 86% of the vaccinates three years after just one injection.⁴⁷ Most rabies vaccines sold are inactivated products that require 2 injections to maximize immune responses. Most cases of rabies in vaccinated animals have been in those only vaccinated once. Several studies now indicate that if a pet has been vaccinated twice for rabies, you are unlikely to acquire rabies. Rabies vaccines are very effective vaccines.⁷³ However, they are responsible for 50% of the vaccine-associated sarcomas in cats.⁵ Kittens should be administered rabies vaccination as per local ordinances and revaccinated 1 year later. Then, the vaccine should not be administered more frequently than every 3 years. A canarypox-vectored rabies vaccine that must be given yearly is now available.⁷⁴ Because this vaccine does not produce chronic inflammation, it should be considered the rabies vaccine of choice for cats. More extended duration of immunity studies are needed to determine whether the vaccine can be can be administered less frequently.