FELINE VACCINATION SCHEDULES: ANOTHER LOOK
Dennis W. Macy, DVM, MS, Professor
Colorado State College of Veterinary Medicine & Biomedical Sciences
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. We must, as responsible health care professionals be able to be just as critical of 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, for a moment, separate monetary motives, advice from accountants, practice managers, etc, whose primary focus is a healthy bottom line, and not -healthy cats, when looking at the medical need for annual vaccination of cats.
Thc current practice in preventative veterinary medicine, which has been "if it is available, give it and give it yearly" is, fortunately changing. As we will see, not all cats need all available vaccines nor do they need any of them annually. Last count, we had rabies, ringworm, panleukopenia, rhinotracheitis, calicivirus, feline leukemia, feline infectious peritonitis, Chlamydia, and the newest kid on the block, Bordetella vaccines for cats. All feline vaccines (all but rabies) are recommended by the manufacturer label to be given annually, Are all these vaccines really necessary for every cat every year? Do you receive all available human vaccines yearly? What is the scientific evidence that the cats immune system is that much different than that of humans. The Feline Practitioners Association, ten colleges of veterinary medicine, American College of Veterinary Internal Medical (oncology specialty), and the United States Army veterinary hospitals worldwide now endorse similar recommendations of a limited number of vaccines. These vaccines are referred to as core vaccines and include feline panleukopenia virus, feline rhinotracheitis virus, feline calicivirus, and rabies virus vaccines to be administered only every three years to adult eats. Non-core vaccines or non-recommended vaccines include Bordetella, feline infectious peritonitis, feline leukemia, Chlamydia psittaci, and Microsporum canis vaccines. The above groups believe that these vaccines should be given only to high-risk groups if at all.
To understand the criteria for vaccine selection and booster frequency recommendations, I believe we must look at the basis of current annual vaccine labeling. Other than rabies, no minimum duration of immunity data is required for veterinary vaccine licensure. The reality of the situation is that a manufacturer of United Stales veterinary vaccines must merely show protection two weeks after the initial vaccine series and the booster recommendation is not required to be based on scientific data and is considered arbitrary! The booster recommendation could just as well be every leap year or full moon! 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 might be really using a three-year vaccine legally relabeled as a one-year vaccine. Unfortunately, there is more truth in labeling required of peanut butter than United States veterinary vaccines. 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. Is the U.S. becoming third world when it comes to veterinary vaccine regulation?
Given the failure of believable manufacturer revaccination label recommendations, conscientious veterinarians are forced to use other criteria to establish frequency of revaccination of cats. Several approaches give the veterinarian more believable information for booster recommendations than the current manufacturer labels. These include the prevalence of a disease, such as panleukopenia, in cats that have ever been vaccinated for this disease at any time in their life, and the duration of immunity provided by natural infection. Most modified live virus vaccines mimic the pathogenesis of the virulent virus and tissue infected by the natural agent and thus may be expected to provide similar protection as the natural infection. Titering, although an indirect measure of protection, can be used for some diseases to determine duration of immunity but have many limitations. Difficulties arise in using titers in that one needs to know the type of vaccine used (MLV or killed), and the pathogenesis of agents that the vaccine is designed to protect against since protection may not be antibody dependent, i.e., titers do not necessarily reflect cellular or mucosal immunity, which can be very important in the prevention of disease. Finally, negative titers do not necessarily equate to susceptibility in previously vaccinated animals and should not be used as the sole basis for revaccination.
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. Another way of performing duration of immunity is by using titers or studying the disease prevalence in previously vaccinated animals living in endemic environments.
Challenge studies have been done for a small group of feline vaccines. In a Cornell study, cats were vaccinated with a killed panleukopenia vaccine, inactivated viral rhinotracheitis and Calicivirus vaccines were held in isolation and periodically bled, and titers to these agents and correlation of the titers to previously published challenge studies are evaluated. In the Cornell study, protective titers were found three years after initial vaccination. These cats were again held in quarantine to eight years following the initial vaccination, titered, and then challenged. Although we cannot yet report the results of this study because it has not been published, investigators have not backed off on the triennial recommendation for cats. Given that each infectious agent is unique and the mechanism of protection may be different for different disease agents, lets approach prevention of disease by infectious agent type. 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.
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. Thc polysystemic infection is potentially deadly to the non-immunized (especially the young), but recovery from natural infection provides life-long immunity. Reports of clinical panleukopenia vaccines have not been reported. Both modified live virus vaccine and killed vaccines provide good antibody responses. Challenge studies in young kittens with maternally derived FPLV antibodies in the immune-vaccinated cat, suggests good protection from virulent challenge in both cases, and correlates with the presence of FPLV serum neutralizing antibody titer. The role of cell-mediated immunity in the protection against FPLV has not been investigated, but cannot be dismissed. The number of long-term antibody studies or challenge trials is limited. In the Ackerman's study in 1983, a killed panleukopenia vaccine demonstrated 100% protection against challenge 25 months after administration of an inactivated panleukopenia vaccine. Reports of serum neutralizing titers have been reported in eight out of eight cats vaccinated with an inactivated FPLV vaccine held in isolation for six years.
Conclusion: Annual revaccination recommendations cannot be supported by natural immunity studies, titer studies, or challenge studies. The new three-year recommendation for panleukopenia is more reasonable, but is still overkill in my opinion. It is doubtful that revaccination after the initial series for panleukopenia is increasing to protection against clinical disease caused by the panleukopenia virus.
Feline upper respiratory disease:
Upper respiratory infection of the cat is caused by feline rhinotracheitis, feline Calicivirus, and Chlamydia psittaci. In general, these agents result in local tissue infections, and seldom result in systemic disease or changes in the cat's hemogram like panleukopenia. All of the above agents develop carrier states to varying degree following infection.
Natural feline rhinotracheitis infections result in transient incomplete immunity in the cat. Mucosal, secretory IgA and cell-mediate immunity are most prominent in protecting cats against FVR. FVR infected cats may recover from clinical disease, but remain persistently infected with intermittent shedding of the virus following periods of stress, but are protected from severe systemic disease. 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. The longest published challenge study has been two months after vaccination in which three out of four challenged cats were determined protected from clinical signs associated with rhinotracheitis. Several long-term persistent FVR, SN titers have been reported with the use of inactivated FVR vaccine. The longest indicated that four out of eight cats vaccinated with inactivated FVR vaccine held in isolation had FVR SN titers six years later. No studies have been done with 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, this would be expected to provide even better protection than killed or inactivated vaccines.
Conclusions:
Either natural infectious, killed, or modified live virus FVR vaccines prevent infection or eliminate shedding, but all reduce deep tissue invasion and the severity of systemic disease as may be expected from the presence of systemic antibody titers. There would appear to be no real justification for annual revaccination for FVR since the greatest protection is likely secretory IgA-related, which probably only lasts several weeks following vaccination. The protection against severe systemic infection and severe morbidity associated with these infections should be our expectations from an upper respiratory vaccine. This expectation is met with the use of inactivated FVR vaccines and lasts over six years! The protection against FVR is most likely much longer and occurs in a greater percentage of vaccinated cats when modified live virus vaccines are used. The three-year recommendation appears conservative, but given the paucity of information on MLV FVR vaccines appears appropriate for now. Like panleukopenia, most losses associated with FVR are in the young, which should be our vaccination targets.
Feline Calicivirus:
Following natural infection with feline Calicivirus immunity to reinfection is believed short, but protection against severe systemic illness is sustained. Cats recovering from Calicivirus disease remain persistently infected with continuous shedding of the virus for months to years. Challenge studies in young kittens with maternally derived FCV antibodies and immune-vaccinated cats, suggests that FVC serum neutralizing titers greater than 1:16 are protective against disease following a virulent challenge. The role of cell-mediated or mucosal immunity in protection against disease has not been established but both are likely to be important. Inactivated FCV vaccine, protection against challenge lasts at least six months and long-term FCV SN titers indicate protective antibody response in eight out of thirteen cats five years following administration of an inactivated FCV vaccine. Modified live FCV vaccines used today are likely to perform even better than the inactivated vaccine used in these studies. The every three-year recommendations appear conservative, but in the absence of more data appropriated for the time being.
Chlamydia psittaci agent results in a moderate to severe conjunctivitis in infected cats. Environmental concerns and poor husbandry practices appear to enhance the likelihood of this infection. The duration of immunity following mature 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. Two studies have shown significant but incomplete protection at 12 months following vaccination with an inactivated vaccine. Chlamydia vaccines do not prevent infection or eliminate shedding, but do reduce clinical signs.
Conclusion:
This is a non-core feline vaccine that should only be used in catteries with a history of chlamydial disease. Veterinarians should address husbandry practices first in all cases. The frequency of use of Chlamydia vaccine is unclear. Like all 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.
Feline leukemia virus:
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. The importance of this information is in our vaccination targeting! The most susceptible are the young. The value of vaccinating adult cats is problematic, with only 10%-15% potentially receiving any true vaccine protection beyond age acquired immunity and the fact that it is one of two vaccines linked to injection site sarcomas, the risk and benefits of vaccination need 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. Since antibody titers have failed to correlate with FeLV vaccine protection, they should not be used in evaluating the need for revaccination of cats for FeLV. Thc selection and use of FeLV vaccine should be based on assessment of risk of infection and risk for development of vaccine-associated sarcoma. Our research suggests the most efficacious FeLV vaccines are the most locally reactive and possibly most likely to be associated with injection site sarcoma development. Given this scenario, our recommendation is only to vaccinate at risk cats and only to give the initial vaccine series and booster at one year. No additional boosters should be given until companies supply more definite data on duration of immunity.
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). However, challenge studies have demonstrated some protection in cats 6 and 12 months following vaccination. Studies have indicated cats must be coronavirus negative at the time of vaccination, have an antibody titer less than 1:100, to receive any benefit from the FIP vaccine. Given that the vaccine only shows a 60-80 preventive fraction at its peak protection time two weeks following vaccination, and the only coronavirus negative < 1:100 receive this marginal benefit from vaccination, and only 1:5,000 cats will die of the disease despite the fact that 20% to 40% of the cat population carrying coronavirus titers greater than 1: 100, limits the recommendation of this vaccine to high risk catteries that are virus negative. 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, then routine FIP vaccination.
Ringworm vaccines:
Ringworm vaccines are inactivated vaccines and oil adjuvanted, which produce significant local reaction at injection sites. This non-core vaccine is best reserved for treatment of ringworm rather than prevention. If ringworm vaccines were used more extensively, they would probably be linked to vaccine site tumor development.
Bordetella vaccine for cats:
The most recent vaccine to be licensed for use in cats (new this year) to prevent disease associated with Bordetella pneumonia in young kittens kept under very poor sanitation. The feline vaccine is basically a toned down version of the intranasal canine Bordetella intranasal version. The duration of immunity is expected to be associated with secretory IgA, thus short-lived as it is in dogs. This is a non-core vaccine that has limited use confined to catteries where documented loss due to Bordetella pneumonia has occurred and should be used in conjunction with improved environmental and sanitary practices. It should be given intranasally to very young kittens only.
Rabies vaccines:
Rabies vaccines are the only veterinary vaccine that requires minimum duration of immunity studies prior to licensure. It should he remembered that these vaccines are tested in young, not fully developed animals and that they still protect 86% of animals three years later following just one injection. Several studies now indicate that if you have had two rabies vaccines in the pet's history, you are more likely to die of lightening than rabies. The bottom line, rabies vaccines are very effective vaccines. The down side is that they are responsible for 50% of the vaccine-associated sarcomas in cats, so they should not be administered more frequently than every three years, and a more extended duration of immunity studies need to be done to perhaps further reduce the frequency of rabies vaccine administration. One exception is the new canarypox rabies vaccine that must be given yearly. Because the canarypox rabies vaccine does not produce chronic inflammation it should be considered the vaccine of choice for cats.
In conclusion, the new feline vaccine recommendations are sound and the triennial frequency may even be too conservative when you consider immunity acquired from natural infection and the immunity to disease in vaccinated humans. Indeed, no one has yet demonstrated significant differences in the immune systems of man, dog and the cat. Why should we continue as a profession to perpetuate the myth of the need for annual vaccination, promoted largely by billion dollar vaccine manufacturers by an arbitrary annual booster recommendation vaccine label. It is time that we critically look at the medical need of these long-standing practices and ask why? We should hold the USDA and vaccine industry to higher standards than we currently have in place. United States veterinarians should not accept third world veterinary vaccine standards for their patients and neither should pet owners who suffer the most from sloppy vaccine regulation. It is not my responsibility or that of others in academia to show the lack of need for annual vaccination, rather, it is the multi-billion dollar vaccine industry's responsibility to provide convincing evidence that cats and dogs are significantly different from humans, and to establish the medical need to administer feline vaccines annually to adult cats to maintain health and I do not mean a healthy bottom line.
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