The report provided here was developed by the AAFP Feline Vaccine Advisory Panel to aid practitioners in making decisions about appropriate care of patients with respect to currently available vaccines. The Advisory Panel included experts in immunology, infectious disease, internal medicine, and clinical practice. As much as possible, the information reported here was based on information from studies in peer-reviewed publications. When such information was not available, the Advisory Panel depended on clinical experience, technical judgments, and results of unpublished studies. Although the information contained herein is intended to be accurate, thorough, and comprehensive, it is subject to change in light of developments in research, technology, and experience. As such, this document should not be construed as dictating exclusive protocols, courses of treatment, or procedures. Other techniques and procedures may be warranted on the basis of the needs of the patient, available resources, and limitations unique to the setting.
The AAFP thanks the members of the Feline Vaccine Advisory Panel for their devotion to this project. The AAFP also appreciates the openness and assistance provided by manufacturers of feline vaccines.
Introduction
Vaccination programs for cats have been major topics of discussion among veterinarians in recent years, primarily because of concerns about vaccine safety, the number of commercially available vaccines, and an incomplete knowledge of the duration and extent of protection provided by certain vaccines.
Vaccines play an important role in the control of infectious diseases. However, some vaccines do not induce complete protection from infection or disease, and they do not induce the same degree of protection in all cats. Exposure to infected animals and infectious agents should be minimized, even in vaccinated cats. The risk of infection and subsequent disease varies with the age and health of the cat, extent of its exposure to the infectious agent and to other cats, and the geographic prevalence of infection. Factors that negatively affect an individual cat's ability to respond to vaccination include interference from MDA, congenital or acquired immunodeficiency, concurrent disease or infection, inadequate nutrition, and immunosuppressive medications. When practical, every effort should be made to ensure that cats are healthy prior to vaccination.
Kittens are generally more susceptible to infection and typically develop more severe diseases than adult cats. Thus, kittens represent the principal target population for vaccination. As part of a routine health care program, the vaccination needs of all cats, including adults, should be assessed at least yearly and, if necessary, modified on the basis of an assessment of a cat's risk.
Vaccination is a medical procedure, and the decision to vaccinate, even with vaccines considered as core vaccines, should be based on a risk-benefit assessment for each cat and each vaccine. Vaccination may indeed be beneficial, but it is not innocuous, and the benefit of vaccinating a cat (ie, the induction of clinically meaningful immunity) must be balanced against the risk of adverse events associated with vaccination. The overall objectives of vaccination, then, are to vaccinate the greatest number of cats in the population at risk; vaccinate each cat no more frequently than necessary; vaccinate each cat only against infectious agents to which it has a realistic risk of exposure, infection, and subsequent development of disease; vaccinate a cat only when the potential benefits of the procedure outweigh the potential risks; and vaccinate appropriately to protect public health.
Core, noncore, and not generally recommended vaccines–Core vaccines are recommended for all cats. The Advisory Panel believes vaccines against FPV, FHV-1, FCV, and rabies virus fall into this category. Noncore vaccines should be administered to cats in specific risk categories as outlined in the section on vaccine antigens. The Advisory Panel believes vaccines against FeLV, FIV, Chlamydophila felis, and Bordetella bronchiseptica fall into this category. Not generally recommended vaccines are those that the Advisory Panel believes have little or no indication; these vaccines have not been found to induce a clinically meaningful immune response in most cats and circumstances, or they may be associated with adverse events out of proportion to their usefulness. The Advisory Panel believes vaccines against FIP and Giardia spp fall into this category.
The Advisory Panel commends veterinary biologics manufacturers for responding to many of the concerns and recommendations in the 2000 report,1 such as inclusion of vaccine antigens in multivalent products on the basis of similar vaccine target populations (ie, similar exposure and infection risks) and similar DOI induced by vaccination (eg, FHV-1/FCV combinations); creation of appropriate monovalent products (eg, FPV vaccines); attempts to develop vaccines that create less inflammation at injectable vaccination sites (eg, nonadjuvanted FeLV and rabies virus vaccines and nonadjuvanted inactivated FPV vaccines); development of novel methods of vaccine administration (eg, transdermal application); development of products with a lower required dosage (eg, IN administered FHV-1/FCV vaccines and recombinant FeLV vaccines); funding of studies to investigate the DOI; licensing of vaccines with DOI > 1 year; exploration of novel vaccine technologies (eg, recombinant vaccines); and desire to work with regulatory agencies to improve vaccine labels and the manner by which adverse events are reported.
Immune Response to Vaccination and Infection
Two major types of immunity prevent or limit infectious diseases: natural (innate) immunity and acquired (adaptive) immunity. Innate immunity, including but not limited to skin, hair, tears, normal microbial flora, mucus, acidity of the stomach, type 1 interferons, neutrophils, macrophages, natural killer cells, and age, prevents most pathogens from infecting and causing disease in animals. Innate immunity is the first line of defense; thus, it is already active or immediately activated in response to inherent or elaborated chemical substances of the infectious agent.2–6
Acquired immunity is characterized by specificity and memory and is stimulated when an animal is vaccinated or exposed to an infectious agent or other antigen. The acquired immune system consists of humoral immunity and cell-mediated immunity. In humoral immunity, differentiated B lymphocytes, called plasma cells, produce the primary feline immunoglobulin classes IgG, IgM, IgA, and IgE.7 Phagocytic cells and effector molecules, such as complement, also play an important role in providing vaccinal immunity. Cell-mediated immunity comprises T lymphocytes, including T helper, T regulatory, and T cytotoxic cells; macrophages; and a number of products of those cells, called cytokines, which all help to provide vaccinal immunity.2,3,7
When a cat is infected or vaccinated, B and T lymphocytes specific for a multitude of antigenic epitopes on viruses, bacteria, and parasites are stimulated to proliferate and differentiate into effector cells. In addition to effector B and T cells that develop and survive for short periods after vaccination, memory B and T cells usually develop to provide long-term immunity. Most of the effector cells themselves are short lived, often surviving only days or weeks after initial stimulation. Memory cells, on the other hand, survive for years, sometimes for the life of a cat. It has been discovered that certain cells continue to produce antibodies for long durations after initial antigenic stimulation such as vaccination. These cells, called long-lived plasma cells or memory effector B cells, persist in the bone marrow for many years and contribute to long-term humoral immunity.8 Similarly, long-lived T-effector cells, or memory effector T cells, probably persist after vaccination or infection with certain pathogens in the absence of overt antigenic stimulation.9 Memory B and T cells and antibodies produced by memory effector B cells cooperate to provide protection from infection at a later time in the life of a vaccinated cat. Immunologic memory is the basis for protective vaccines.10 Cell-mediated immunity and humoral immunity are stimulated in minutes to hours (anamnestic response) when a vaccinated cat is exposed, whereas it often takes days to weeks (primary response) for immunity to be stimulated in a nonvaccinated, immunologically naive cat.10–13
Whether cell-mediated or humoral responses are most important for mediation of protection varies with the specific pathogen, the route of infection, and the colonization and replication of the infectious agent. For instance, many pathogens of the respiratory or gastrointestinal tract require generation of mucosal cellular or humoral immune responses, with IgA being the most effective and abundant antibody class on mucosal surfaces of cats.14 On the other hand, systemic infections are controlled or prevented primarily by IgG and circulating effector T cells.5,9
If vaccination prevents subsequent infection, the animal is considered to have sterilizing immunity, the ultimate form of immunity because disease cannot develop. This form of immunity may develop after immunization against FPV and rabies virus. When vaccination does not prevent infection (eg, FHV-1 and FCV), systemic and local cell-mediated immunity and humoral immunity, including local IgA antibodies, play important roles in preventing or reducing the severity of disease.2,5,9
Duration of Immunity
Few independent studies investigate the DOI induced by feline vaccines (for additional information, see the section on vaccine antigens). In immunologic terms, DOI is the duration that immunologic memory persists to provide protection from infection or disease at the time of natural challenge. In regulatory terms, establishing DOI means demonstrating to the satisfaction of a regulatory agency that efficacy is demonstrated when challenge occurs at a specific point in time after vaccination. The USDA CVB requires manufacturers to perform efficacy studies that correlate with the time frame referenced on the label for rabies vaccines and all novel antigens, which are antigens that were not licensed prior to 1994. This requirement does not apply to most feline vaccines currently in use. In the absence of DOI information for each product, veterinarians may rely on guidelines for each vaccine, such as those provided here. In the European Union, a minimum DOI must be determined for each product on the basis of controlled experimental challenge and field trials.15
Tests to predict immunity–Measurement of specific systemic immune responses to an infectious agent may potentially predict resistance to infection or disease and determine whether vaccination is required in an individual cat, provided the appropriate immune response can be accurately measured.16 In most infections in cats, the presence of serum antibodies against an infectious agent indicates that the cat has the immunologic memory required for a rapid anamnestic immune response if the cat is subsequently exposed. In many mucosal (eg, respiratory or gastrointestinal tract) infections, local immune responses, particularly the presence of secretory IgA antibody, are most effective at preventing infection or disease.14 Unfortunately, mucosal immune responses cannot be easily determined in a clinical setting, and direct determination of cell-mediated immune responses cannot be currently performed in a clinical setting. However, detection of serum antibodies against an infectious agent is an indirect measure of memory B and T cells and memory effector B cells that are required for protective immunity because responses to all complex vaccine antigens require both B- and T-cell activation.2,3,5,17
Information relating vaccine-induced serum antibody responses with resistance to infection has been collected primarily for FPV, FHV-1, and FCV. For FPV, serum antibody titers as determined by validated viral neutralization, hemagglutination inhibition, or ELISA techniques can be used to predict resistance to both infection and disease.18–21 Results of 2 studies20,21 indicate that all cats with antibodies against FPV as a result of vaccination within the previous 7 years were protected against the USDA challenge strain and dose of FPV. However, because vaccination for FCV and FHV-1 does not prevent infection, but only lessens the severity of clinical disease when exposure to virulent virus occurs, the predictive value of serum antibody titers for determination of vaccination need is less clear than for FPV. In cats vaccinated with a commercially available modified-live agent product or a killed agent product 30 to 36 months earlier, detection of virus-specific antibodies against FCV and FHV-1 (as determined by virus neutralization and ELISA) was predictive of disease resistance following challenge with USDA challenge viruses.20 In that study,20 all cats with detectable antibodies against FCV and most cats with detectable antibodies against FHV-1 (91.3% via virus neutralization; 90.5% via ELISA) had > 50% reduction in magnitude of clinical signs, compared with unvaccinated control cats.
Virus neutralization antibodies against FeLV can be measured (although tests are not commercially available), but their presence in a vaccinated cat does not always predict resistance to infection; presence in a nonvaccinated cat indicates that the cat either was or is infected.
For most cats, the Advisory Panel recommends using revaccination intervals as described herein rather than measuring antibody titers. However, if antibody testing is used in lieu of set revaccination intervals for FPV, FCV, and FHV-1, the following points should be considered:
If previous vaccination history is not available, core vaccines should be given.
Antibody test results from all laboratories cannot be assumed to be equivalent; practitioners are cautioned to only use laboratories that have validated their test results.
Virus neutralization assays document in vitro inactivation of the specific virus by serum antibodies. An ELISA can be designed to measure antibodies against viral antigens, but positive results do not necessarily indicate that the antibodies neutralize the virus. Thus, only tests for which results have been found to predict protection should be used.
Serologic testing for assessment of vaccine need should be reserved for previously vaccinated adult cats. If circumstances require measurement of antibodies in kittens younger than 16 weeks of age, a sample should be collected on the day of vaccination and a second sample should be collected 2 or more weeks later. An increase in antibody titer indicates that vaccination induced an immune response.
Detection of serum antibodies against FPV, FCV, and FHV-1 by validated assays appears to predict resistance to disease in most cats. Failure to detect serum antibodies does not necessarily indicate susceptibility, but it would, in most cases, be an indication that the cat may benefit from revaccination.
Types of Vaccines
The immune response induced by natural infection depends on the type of antigen, route of entry, primary site of infection, and pathogenic mechanisms. These same factors must be considered when a vaccine is given to induce an effective immune response.
Various types of feline vaccines are commercially available (Table 1). The most common vaccines currently in use are infectious vaccines, which include modified-live agent vaccines and live virus-vectored recombinant vaccines, and noninfectious vaccines, which include inactive (killed) whole-organism vaccines and subunit vaccines.
Feline vaccines currently available in the United States.
Feline vaccines currently available in the United States (continued).
Modified-live agent vaccines consist of avirulent or attenuated organisms that infect the host. In cats, some are formulated to be given by injection; others are designed to be administered IN. Modified-live agent vaccines are capable of stimulating serum antibodies, local mucosal antibodies, and systemic and local cell-mediated immune responses, depending on the route of administration, and create immunity similar to that induced by recovery from natural infection.4,5,10,23,24
The USDA currently recognizes 3 categories of recombinant vaccines for use in veterinary medicine: category 1 products comprising inactivated recombinant organisms or purified antigens derived from such organisms (eg, subunit vaccines), category 2 products comprising live organisms with deleted genes (eg, gene-deleted vaccines), and category 3 products comprising live vectors expressing heterologous genes for immunizing antigens (eg, live virus-vectored vaccines).23 Chimera is an additional term soon to be applied to certain recombinant veterinary vaccines.25 All vaccines rely on antigen presentation by antigenpresenting cells (eg, macrophages and dendritic cells) to initiate an immune response. With category 3 recombinant vaccines, nonpathogenic virus vectors replicate in a limited way and cause antigen-presenting cells to express products of genes (specific proteins unique to the pathogenic virus or bacteria) inserted into the vector's genome, thereby inducing an immune response to an organism. Recombinant vaccines may or may not contain adjuvant; however, none of the virus vectored vaccines currently licensed for cats by the USDA are adjuvanted.
Killed agent vaccines frequently contain adjuvant (usually a chemical in companion animal vaccines) to enhance the immune response. Adjuvanted FeLV and rabies virus vaccines have been associated with local inflammatory reactions at injection sites, with the degree of inflammation varying among products.a The potential role of local inflammatory reactions in the genesis of vaccine-associated sarcomas remains controversial (see section on adverse events and reporting). In general, the response to killed agent vaccines is slower than that induced by infectious vaccines24; however, studies indicating that this is true for all feline vaccines are lacking. The immunity induced by killed agent vaccines is predominantly, but not exclusively, systemic antibody with little or no IgA antibody on mucosal surfaces, and cell-mediated immunity is limited to type 1 T–helper cell immunity. Immunity induced by killed agent vaccines is therefore less likely to provide effective levels of secretory IgA or complete cell-mediated immune protection at mucosal surfaces in the respiratory and gastrointestinal tracts.5,14
Each vaccine type has advantages and disadvantages in addition to those aforementioned. For example, properly manufactured killed agent vaccines (eg, not contaminated with live agents) cannot cause the diseases for which they are designed to prevent; inactivated agent vaccines may therefore be preferable in disease-free colonies, such as research facilities housing SPF cats. Although infectious agents in modified-live agent products have been attenuated, normal host immune responses are required if vaccinates are to resist disease from attenuated organisms. Thus, attenuated agents in severely immunosuppressed or genetically susceptible hosts may result in the disease for which the vaccine was designed to prevent. In the early 1980s, several cats vaccinated with attenuated rabies virus vaccines developed rabies.26,27 Furthermore, a live attenuated agent may revert to virulence, causing disease even in cats that are not immunosuppressed. On the other hand, some inactivated agent vaccines are more highly associated with inflammatory reactions at vaccine sites than are modified-live agent vaccines.15
Although multiple manufacturers may produce a vaccine designed to protect against a specific disease, vaccines are not all the same. A careful review of individual labels and package inserts is necessary to distinguish 1 vaccine type from another.
Routes of Administration
Numerous routes are approved for administration of feline vaccines. For some infectious agents (eg, FPV, FHV-1, and FCV), vaccines administered via injection and IN routes are available in some parts of the world. Depending on the properties of the infectious agent and the situation in which the product will be applied, a particular route of vaccine administration may be advantageous. Vaccines must be administered by routes stipulated by the manufacturer in the package insert; the consequences of administering a vaccine by any route not evaluated and recommended by the manufacturer may impair the health of the patient.
Injection–Most injectable feline vaccines are licensed for administration by SC or IM injection. There is no evidence that the risk of vaccine-associated sarcomas is decreased in cats vaccinated by the IM route; in fact, development of a sarcoma in muscle may delay detection. Additionally, although 1 manufacturer may offer the option of either SC or IM administration, it should not be assumed that these routes apply to a vaccine containing the same antigens but produced by a different manufacturer.
IN administration–Immunity against many pathogens of the respiratory or gastrointestinal tract requires generation of mucosal cellular or humoral immune responses. However, this varies by agent. Viruses and bacteria that effectively replicate in the respiratory tract will generally produce an effective local and systemic immune response. Feline calcivirus, FHV-1, and B bronchiseptica replicate locally in the respiratory tract, and vaccines designed for IN administration are available for each of these agents. Vaccines administered IN are also available for FPV and FIP; the reader is referred to the section on vaccine antigens for additional discussion.
Transdermal administration–A recombinant canarypox-vectored FeLV vaccine licensed in the United States is only approved for administration by use of the manufacturer's transdermal administration system; SC or IM administration of this vaccine by use of needle and syringe is expected to result in a suboptimal immune response. This is in contrast to a recombinant FeLV vaccine available in the European Union that is given by SC injection.
Special Considerations
Many factors can negatively influence a cat's ability to respond to vaccines. Routine physical examination and FeLV and FIV testing prior to administration of vaccines is important to determine such factors as age, preexisting illness or infection, and alterations of immune status, all of which should be considered when developing a vaccination protocol. The level of challenge dose may also influence the efficacy of a vaccine in an individual. Thus, additional vaccinations might be considered in situations where, for example, a previously low-risk cat enters a high-risk situation.
Age Kittens–Immunity existing at an early age includes innate immunity (which is often not as effective in young kittens), MDA, and actively acquired humoral and cell-mediated immunity induced by effective vaccination or recovery from natural infection.
Although the immune response may not be as robust in young kittens, it is important to vaccinate kittens at an early age in an attempt to induce immunity prior to their first exposure to the pathogen. An important cause of vaccine failure in kittens is the presence of MDA. In most situations and most diseases, MDA in most kittens is lost by 9 to 12 weeks of age. However, in some cases in which maternal antibody titers are low or in which there was inadequate transfer of colostrum, kittens may lose their MDA by 6 weeks of age or earlier and thus be capable of responding to vaccination at this early age. In kittens born to queens with high antibody titers (eg, through natural exposure), MDA may last for as much as 16 weeks; results of 2 studies28,b suggest that some kittens will not be protected by a final vaccine given at 12 to 14 weeks of age. Although studies indicating the age at which all vaccinates will be protected have not been performed, it is prudent to ensure that the final vaccine in the initial series be given to kittens no sooner than 16 weeks of age. In most situations, revaccinating every 3 to 4 weeks until kittens attain that age is sufficient.
There is no evidence that vaccination of kittens every 2 weeks results in an impaired immune response, and although such frequent revaccination of kittens is not necessary or cost effective in most cases, kittens in high-risk environments (eg, panleukopenia-endemic shelters or catteries) may benefit from being vaccinated this frequently as long as they remain in the environment or until 16 weeks of age, whichever comes first. A single dose of modified-live agent vaccine should, in theory, suffice for initial vaccination of cats older than 16 weeks of age. Nonetheless, to increase the likelihood of immunization in this group of cats, the Advisory Panel recommends that 2 doses of vaccine, whether killed agent or modified-live agent, be administered. The 2 doses should be given at an interval of 3 to 4 weeks and not < 2 weeks.
Analysis of data from the SARSS15 in the United Kingdom found that kittens < 6 months old were over-represented for adverse events associated with vaccination, compared with older cats.15 This may be a real effect or it may reflect a high reporting rate by owners. It may also be attributable in part to the coincidental onset of age-related diseases or infection with naturally occurring viruses.
Other potential causes of vaccine failure in kittens include stressors such as early weaning and changes in environment, concurrent illnesses, parasites, nutritional inadequacies, and exposure to high numbers of pathogens in multiple-cat environments (eg, shelters and breeding catteries). However, the true impact of these stressors is not known.
Senior cats–Whether older cats respond in the same manner to vaccination as do younger cats has not been adequately studied. In the absence of data, the Advisory Panel recommends that healthy older cats and those with chronic but stable disease conditions receive vaccines in the same manner as young adults.
Breed
In the United Kingdom, analysis of the SARSS database revealed that pedigree cats, especially Burmese and semilonghair cats (a category that includes Birmans and Maine Coons), were overrepresented for vaccine adverse events, compared with non-pedigree cats.15 This could be a real effect, with some breeds being more predisposed than others to reactions after vaccination. However, it may also reflect greater use of vaccines in pedigree cats than nonpedigree cats, with pedigree cat owners being more inclined to report any reactions seen. Similar information is not available for cats in the United States.
Vaccination in breeding catteries
Vaccine schedules reported here are appropriate in most cats. Queens in which the vaccination status is not adequate or that have a prior history of infection with FHV-1 or FCV may receive booster vaccines prior to breeding or parturition to maximize delivery of MDA to kittens.29,30 Unless specifically stated on the label, vaccines are not evaluated by manufacturers for safe use in pregnant queens, and routine vaccination of pregnant cats should be avoided. However, the benefits of vaccinating a pregnant queen may outweigh the risks in some circumstances (eg, catteries with endemic URD). If vaccination is determined to be essential, use of killed agent vaccines may be preferable. Use of products labeled for IN administration in kittens in shelters (see section on vaccination in shelters) is appropriate in catteries with endemic viral URD.
Vaccination of lactating queens
Lactation is not known to interfere with the immune response to vaccines. However, administration of any vaccine may stress the queen, even in the absence of vaccine-associated adverse events, and may result in a temporary deterioration of mothering ability and milk production. Thus, in general, use of vaccines in lactating queens should be avoided. In shelter environments, however, it is advisable to vaccinate all cats with modified-live agent vaccines, including lactating queens, at the time of admission, as the benefits of vaccination (protection of the queen from disease) likely outweigh the risks of vaccine-induced disease (eg, possible FPV vaccine virus shedding to kittens younger than 4 weeks old).
Vaccination of cats with preexisting illness
Manufacturers evaluate vaccine efficacy in healthy cats and, accordingly, vaccines are labeled for use in healthy cats only. However, the Advisory Panel acknowledges that in certain circumstances, vaccination of a cat with chronic but stable illness may be justified. Whether a vaccine should be administered to an ill patient is at the discretion of the veterinarian.
Cats with acute illness, debilitation, or high fevers should not be vaccinated. However, in shelters or other multiple-cat environments in which delaying vaccination may lead to increased susceptibility to infection, vaccination in the face of illness may be indicated. Vaccination of cats in shelters with injuries or mild to moderate illness (such as URD or dermatophytosis) with FPV, FHV-1, and FCV is advised on admission. Vaccination of cats not in shelters, yet with severe disease, should ideally be delayed until the cat has recovered from the illness.
Vaccination of retrovirus-infected cats
Retrovirus-infected cats should be housed indoors and isolated from unvaccinated cats to diminish their likelihood of infecting others and to reduce their exposure to other infectious agents or trauma. The Advisory Panel recommends that core vaccines (FPV, FHV-1, FCV, and rabies virus) be administered to FeLV-infected cats; noncore vaccines should be given only if the risk of patient exposure justifies their use. Cats infected with FeLV may not be able to mount adequate immune responses to vaccination against rabies virus and perhaps to other vaccines as well.c Therefore, protection induced by vaccines in FeLV-infected cats may not be comparable to that achieved in uninfected cats.
Experimental evidence indicates that FIV-infected cats are capable of mounting immune responses to administered antigens, except during the terminal phase of infection, although these responses may be delayed or diminished.31–35 Results of studies32,36 to determine whether immune stimulation (eg, vaccination) accelerates the course of FIV-induced immunodeficiency are conflicting, but a potential trade-off to protection from disease by vaccination is progression of FIV infection secondary to increased viral production. The Advisory Panel recommends that core vaccines be administered to FIV-infected cats, but noncore vaccines should be given only if the risk of patient exposure justifies their use. In 1 study,37 cats experimentally infected with FIV developed vaccine-induced panleukopenia when given modified-live FPV vaccines. Whether cats naturally infected with FIV are at increased risk of developing vaccine-induced disease from residual virulence of infectious vaccines is not known; however, administration of noninfectious vaccines is preferred whenever available.
In shelter environments, cats destined to be group housed with other cats should be appropriately tested for FeLV and FIV prior to inclusion.38 Retrovirusinfected cats should be housed separately from uninfected cats and sent off-site for more appropriate care (such as spaying or neutering) as soon as possible. Because of their high risk of exposure, FIV-and FeLV-infected cats should receive killed FPV, FHV-1, and FCV vaccines when maintained in a shelter. Rabies virus vaccine should be administered to all cats that are placed at the time they are discharged from the shelter.
Concurrent use of corticosteroids
Depending on dosage and duration of treatment, corticosteroids may cause functional suppression of immune responses, especially cell-mediated responses; however, studies examining vaccine effectiveness and safety in cats receiving corticosteroids are lacking. In dogs, corticosteroids do not appear to result in ineffective immunizations when given for short durations at low to moderate doses.39 Comparable studies have not been performed in cats; nonetheless, concurrent use of corticosteroids at the time of vaccination should be avoided if practical.
Vaccination of cats with prior vaccine-associated adverse events
Vaccination of cats with prior vaccine-associated adverse events should be undertaken only after serious consideration of the risks and benefits. In such patients, vaccination may be more life threatening than omitting vaccination altogether. Determination of antibody titer would be useful to assess immunity to core vaccines.
The clinical signs of allergic reactions in cats are different from those in dogs. Of those reported to the US Pharmacopoeia Veterinary Practitioners' Reporting Program during the time it was operational, 66% involved the gastrointestinal tract (usually vomiting, with or without diarrhea), 22% involved the respiratory tract (eg, dyspnea), and 12% involved the skin (eg, urticaria). These signs may progress to hypotension and cardiovascular collapse if untreated. No trend suggesting an association between anaphylaxis and any particular brand or type of vaccine was evident.40
In cats that have had vaccine-associated sarcomas, if practical, injectable vaccines should not be administered again. Cats having developed anaphylaxis with prior vaccination should not receive the same product again, but the extent to which the risk of severe reactions is mitigated by use of a different product, type, or route is not known. If revaccination is determined to be more beneficial than harmful, only 1 vaccine should be administered. If other vaccines are to be administered, they should be given no sooner than 3 weeks later and only 1 vaccine should be given at each time. The cat should then be monitored in the hospital for 4 to 6 hours after vaccination. For mild reactions, the Advisory Panel suggests that antihistamines (eg, diphenhydramine HCl administered at a dose of 2 mg/kg, IM) and corticosteroids (eg, dexamethasone administered at a dose of 5 mg, IM) be administered 20 minutes prior to vaccination; however, the ability of these medications to blunt an adverse reaction has not been adequately investigated.
Rabies virus vaccines are particularly problematic if previously associated with an adverse event because in many parts of the world, the law requires them. In situations in which vaccination is legally mandated yet may endanger the health of the cat, a certificate of exemption may be signed by the client and veterinarian in lieu of vaccination. A copy of the certificate should be given to the client and a copy maintained in the patient's permanent record. Text used in New York State is included as an example (Appendix 1).
Suggested vaccination intervals
Studies addressing minimum and maximum vaccination intervals for cats receiving the initial vaccination series have not been published. The Advisory Panel recommends the following:
Primary vaccination of kittens–Vaccines should be administered at intervals of 3 to 4 weeks until kittens are 16 weeks old. In general, the series is started at 8 to 9 weeks of age; however, under mitigating circumstances (eg, in shelters and catteries with endemic URD), vaccination may begin as early as 6 weeks of age. The minimum vaccination interval during the primary series is 2 weeks, and the maximum recommended interval is 4 weeks. Kittens presented for booster vaccination 6 weeks or longer following administration of the previous dose of vaccine should receive at least 2 doses of vaccine, 3 to 4 weeks apart.
Rabies virus vaccines should be administered in accordance with local or state statutes. In locations in which rabies virus vaccination is not required, the Advisory Panel suggests that kittens receive a single dose of rabies virus vaccine between 12 and 16 weeks of age (as early as 8 weeks of age, depending on vaccine type); a booster vaccine should be administered 1 year later.
Primary vaccination of adult cats–Cats older than 16 weeks of age that are evaluated for initial vaccination should receive 2 doses of vaccine at an interval of 3 to 4 weeks and not < 2 weeks.
Booster vaccination–Recommended vaccination intervals for cats receiving booster vaccines are summarized (Table 2). Once the initial vaccine series has been completed, the Advisory Panel believes a single dose is sufficient for cats evaluated for revaccination beyond the suggested interval for booster vaccination.
Summary of vaccination of cats in general practice.
Summary of vaccination of cats in general practice (continued).
Summary of vaccination of cats in general practice (continued).
Summary of vaccination of cats in general practice (continued).
Vaccine Antigens
FPV
Agent–Feline panleukopenia is an often fatal disease found worldwide and caused by FPV infection. Clinical signs of disease include lethargy, anorexia, vomiting, diarrhea, fever, and sudden death. Disease is often accompanied by a profound panleukopenia, and mortality rates are high in young, susceptible cats.41 In utero infection with FPV can cause cerebellar hypoplasia,42 and as cerebellar development continues during the first 2 weeks after birth, infection in young neonates may also occasionally result in the condition. Feline parvovirus is highly contagious, remains stable and infectious for months to years in the environment, and is primarily spread via the fecal-oral route. Fomites (eg, cages, food bowls, litter boxes, and health care workers) play an important role in transmission of the organism, as can buildup of the virus in a contaminated environment.
Canine parvovirus type 2 emerged as a canine pathogen probably from mutation of FPV or another closely related parvovirus. Canine parvovirus type 2 initially lacked the ability to infect cats, but CPV-2 variants have now emerged (CPV-2a, CPV-2b, and CPV-2c) that have largely replaced the original CPV-2, and these do have the ability to infect cats and, in some cases, to cause clinical parvoviral disease.43,44 Results of cross-neutralization and challenge studies43,45,46,d suggest that FPV vaccination affords good protection against these CPV-2 variants; however, further studies are needed to confirm these observations.
Diagnosis of infection–A presumptive diagnosis of FPV infection is often made on the basis of appropriate clinical signs with profound leukopenia detected on CBC. Detection of a rise in antibody titer during a 2-week period may help to confirm the diagnosis, as may the detection of virus, viral antigen (as determined via ELISA), or viral genetic material (as determined via PCR assay) in fecal samples.e Histologic examination of tissues usually reveals characteristic lesions in the small intestine, which are virtually pathognomonic, and viral inclusion bodies may be detected in infected cells.
Vaccination–Immunity conferred by FPV vaccines is considered to be excellent, and most vaccinated cats are completely protected from clinical disease. Both antibody titer and challenge exposure data indicate that an FPV vaccine for administration via injection induces immunity that is sustained for at least 7 years.19,21 Modified-live and inactivated FPV vaccines for injectable administration and, in some countries, MLV vaccines for IN administration are available and effective. Results of studies indicate that IN administration of CPV-2 vaccines to puppies is less effective than parenteral administration in overcoming maternal antibody interference,f possibly resulting from fewer virus particles reaching and replicating in lymphoid tissue. Although similar studies have not been performed in cats, the same phenomenon could occur in this species as well. Experience with naturally occurring disease suggests IN vaccination may not be as effective as SC vaccination in high-risk environments in which exposure may occur soon after vaccination.f,g
Maternally derived antibody may interfere with immunization when antibody titers are high during the neonatal period, and kittens will be at greatest risk of infection in the period between waning MDA and effective vaccine-induced immunity. Maternally derived antibody titers generally wane sufficiently to allow immunization by 8 to 12 weeks of age.47,48 However, there is considerable interindividual variation,28 and no single vaccination schedule will be appropriate for all kittens. A proportion of kittens will have low to no MDA titers and may respond to vaccination at 6 weeks of age28; thus, early vaccination may be appropriate, especially in situations of high risk and questionable MDA status (eg, rescue catteries). Nevertheless, some cats will have sufficient MDA to prevent effective vaccination before 12 weeks of age or possibly older in some situations. In 1 study,28 only 67% of kittens were protected after receiving 2 to 3 FPV vaccines before 12 weeks of age because of MDA. In another study,b 75% of kittens with preexisting MDA that received a modified-live FPV vaccine at 8, 11, and 14 weeks of age developed protective titers by 17 weeks of age.
Adverse events associated with vaccination– Serious adverse events associated with FPV vaccines are rare. Vaccination of pregnant queens with modified-live FPV vaccines may result in neurologic disease in developing fetuses; the same concern applies to kittens vaccinated at 4 weeks of age.49,50 Therefore, the use of modified-live FPV vaccines should be avoided in pregnant queens and kittens < 4 weeks old,51,52 although use of modified-live FPV vaccines in pregnant cats in rescue shelters may be beneficial (see section concerning vaccination in shelters).
Advisory Panel recommendations–Because of its ubiquitous nature and serious disease-causing potential, FPV vaccines should be considered as core vaccines. Following the initial series of vaccinations (beginning as early as 6 weeks of age and repeated every 3 to 4 weeks until 16 weeks of age), cats should be revaccinated 1 year later. Thereafter, cats should be vaccinated no more frequently than once every 3 years.
Shelter considerations–Feline parvovirus vaccines should be considered as core vaccines in shelters. Kittens should be vaccinated beginning at 4 weeks of age during an outbreak and at 6 weeks of age otherwise.28 The Advisory Panel recommends that modified-live FPV vaccines be used instead of inactivated vaccines because of their quick onset of immunity and greater efficacy at overcoming maternal antibody.53 Feline parvovirus vaccines administered via injection should be used in a shelter environment instead of or in addition to vaccines administered IN, as they provide more consistent protection in a contaminated environment and may be better at overcoming MDA interference.53 Although concerns have been raised regarding reversion to virulence when many vaccinated cats share a litter box, this has never been documented.24 Modified-live FPV vaccines should be given by injection to cohoused cats and kittens, regardless of the number of animals housed together. Vaccination should be repeated every 3 to 4 weeks (every 2 weeks in high-risk environments) in kittens until 16 weeks of age. If adult cats are ill or otherwise compromised at the time of initial vaccination, consider repeating the vaccine once when the cat is in good health (no sooner than 2 weeks after administration of the initial vaccine).
FHV-1
Agent–Feline herpesvirus-1 is an important cause of URD in cats.54,55 Feline herpesvirus-1 occurs worldwide, and it is likely that most cats will be exposed to infection. There is only 1 serotype of the virus, and genetically, all isolates are similar. Typically, FHV-1 induces mild to severe URD. The disease is generally self-limiting, although some cats may develop chronic clinical signs of URD. Occasionally, generalized disease may develop, particularly in young or immunosuppressed cats. In addition, the role of FHV-1 in various forms of ocular disease and skin lesions is increasingly being recognized and evaluated.56–59
All ages of cats are susceptible, although disease may be more severe in young kittens. Upper respiratory tract disease is common in groups of cats, such as in some boarding facilities, pedigree catteries, and rescue shelters, in which stress may lead to virus reactivation and spread from carrier cats; in addition, rapid, high-dose exposure may lead to a shorter incubation period and severe clinical signs.55,60,61 In breeding colonies, disease tends to be seen in young kittens following the decline of MDA. This generally develops by 9 weeks of age but may develop earlier.28,55
Virus is shed in the oropharyngeal, conjunctival, and nasal secretions of infected cats. Transmission is mainly by direct cat-to-cat contact, but indirect transmission may occur via contamination of the environment or fomites.54,55 However, the virus is relatively labile in the environment, remaining infectious for 24 hours. Aerosol transmission is not of major importance, although sneezed macrodroplets may transmit infection over short distances. Acutely infected cats shed virus for 1 to 3 weeks, after which most, if not all, become lifelong, latently infected carriers. In a proportion of such carriers, reactivation can occur following periods of stress or corticosteroid treatment, and these cats may then transmit infection.54,55 During such episodes, carrier cats may have clinical signs of disease.
Diagnosis of infection–Diagnosis of FHV-1 infection has classically been confirmed by virus isolation in cell culture from oropharyngeal or conjunctival swab specimens, although immunofluorescence has also been used. Increasingly, PCR assay is being used because it is significantly more sensitive than traditional methods59,62–65; however, test sensitivity varies greatly.66 In addition, because FHV-1 can be shed both by clinically normal cats as well as cats with disease, viral detection by PCR assay (or other techniques) will not necessarily confirm the cause of disease.66
Vaccination–Modified-live and inactivated FHV-1 vaccines for injection are commercially available, and in some countries, MLV vaccines for IN administration are also available. Both MLV and inactivated virus vaccines provide reasonable protection against disease but do not prevent infection or viral latency. Inactivated virus vaccines may be more appropriate in disease-free colonies because there is no risk of spread or reversion to virulence.
Maternally derived antibody in most kittens is undetectable by 9 weeks of age, but there is considerable interindividual variation, and in some individuals, MDA may still be at interfering concentrations at 12 to 14 weeks of age.28,b A proportion of kittens will have low to no MDA titers and may respond to vaccination at 6 weeks of age28; thus, early vaccination may be appropriate, especially in situations of high risk and questionable MDA status (eg, rescue catteries). Vaccines for IN administration offer rapid (2 to 6 days) onset of protection in naïve cats and can be useful for cats entering a high-risk situation, such as a boarding facility or shelter.54,55,67 Although not licensed for such use, where disease is endemic, vaccines for IN administration have been advocated in kittens younger than 6 weeks old, and results of several studies28,68 indicate that vaccines for injectable administration may be effective starting at 5 to 6 weeks of age.28,68 Results of 1 study69 indicate that vaccination during pregnancy can help protect kittens by prolonging MDA; vaccination in this manner is not generally recommended but may be considered in multiple-cat environments with endemic URD and housing pregnant cats (eg, some breeding catteries and shelters).
Results of serologic and challenge studies19–21,70 indicate that there is likely to be reasonable protection in most cats for as much as 3 years or longer after vaccination. However, protection is not always complete immediately following vaccination and may decline as the vaccination interval increases.18,21
Adverse events associated with vaccination– Modified-live FHV-1 vaccines for injectable administration, invariably used in combination with FCV vaccines, are generally safe, although mild clinical signs may occasionally develop after their use.15 In some cases, this may result from accidental oronasal expo