Vaccines, including those from different manufacturers that are licensed to protect against the same pathogen, should not be assumed as equivalent. Differences in processes and technology used to produce vaccines, as well as additives such as adjuvants, and vaccine route of administration influence efficacy, safety, and duration of immunity. Vaccines may be inactivated, attenuated live, or recombinant (See table 1 below).

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 All veterinary vaccines, before licensing, are assessed for efficacy, safety, potency, and purity. Vaccine efficacy is often expressed as preventable fraction, defined as the proportion of vaccinated animals that do not develop a disease after challenge (so-called sterilizing immunity, e.g., FPV, FeLV, and rabies vaccines), compared with unvaccinated animals that do develop the disease. It can also be expressed as mitigatable fraction (proportion with reduction in severity of clinical signs, e.g., FHV-1 and FCV vaccines). Other claims include reduction of pathogen shedding, prevention of a specific clinical sign, or prevention of mortality. The level or degree of protection claim can therefore be limited.

Inactivated vaccines are vaccines in which the target pathogen is “killed” and therefore unable to replicate in the host. Although these vaccines are unable to revert to virulence, they often contain adjuvants and other excipient proteins to promote an adequate immune response, which have been implicated in acute and delayed adverse reactions in cats. Inactivated vaccines produce weaker immune responses of shorter duration when compared with attenuated live vaccines, and more frequent booster immunizations may be required (generally annually). With the exception of rabies, two initial doses of vaccine 3–4 weeks apart in the absence of MDA are absolutely essential to produce an effective immune response, and if more than 6 weeks elapses between these doses, it is recommended in other guidelines reports that the series be repeated.^2,8 Full protection may not develop until 2–3 weeks after the last dose. Inactivated vaccines are generally considered safer than attenuated live vaccines for use during pregnancy and in immunosuppressed animals, although systemic allergic reactions could still jeopardize pregnancy.

Attenuated live vaccines  (modified-live vaccines) contain microorganisms that are artificially manipulated so as to reduce their virulence or are field strains of low virulence. Repeated passage through cell culture is the most common means of attenuation. Because organisms in attenuated live vaccines replicate in the host, they stimulate an immune response that more closely mimics protection from natural infection. There is generally a more rapid onset of immunity than with inactivated vaccines, and, in the absence of MDA, only one dose of vaccine may be sufficient to provide protection. Partial immunity after vaccination with a single dose of attenuated live FPV vaccines can occur within hours.^9–11 In addition, live vaccine organisms that are shed can immunize other animals in a population. However, the potential for vaccine organism– induced disease exists. This is most likely to occur in immunosuppressed animals, such as neonates that are younger than 4 weeks old. In addition, use of attenuated live vaccines is more likely to result in the generation of false-positive results as indicated by diagnostic tests that are designed to detect the target pathogen (antigen or nucleic acid). With prolonged shedding of live vaccine organisms, this can be a problem for weeks after vaccination. All bacterial and viral vaccines licensed for intranasal administration in cats are attenuated live, as are a number of parenteral vaccines.

Recombinant vaccines are created through manipulation of the deoxyribonucleic acid (DNA) of a pathogen in the laboratory, with reduction in pathogen virulence. Types of recombinant vaccines include subunit, deletion mutant, vectored, and DNA vaccines. Currently, the only available recombinant vaccines for cats in North America are vectored vaccines, which use a recombinant canarypox virus as a vector. In these vaccines, DNA of the pathogen that encodes for an immunogenic antigen is incorporated into the canarypox genome, which then undergoes aborted (limited) replication in the host with expression of the immunogen, in turn inciting a protective immune response. Compared with inactivated vaccines, canarypox vectors offer a more rapid onset of immunity and may be more effective in the face of persistent MDA. Canarypox-vectored vaccines also do not require adjuvant and have been associated with a reduced risk of injection-site sarcomas in cats.¹² However, one study suggested that the degree of protection induced by the recombinant canarypox FeLV vaccine may not be as robust as that induced by whole inactivated FeLV vaccines,¹³ which might produce sterilizing immunity.¹⁴ However, moderate to severe immunosuppression may have impacted the results, so further studies are required to determine whether a clinically important difference exists.

To facilitate vaccine selection, vaccines for dogs and cats have been divided into core vaccines, non-core vaccines, and those generally not recommended. Core vaccines are for all cats with an unknown vaccination history. The targeted diseases cause significant morbidity and mortality and are widely distributed. In general, vaccination for core diseases results in good protection. 

The not generally recommended category of vaccines pertains to diseases of low clinical significance or that respond readily to treatment; vaccines for which evidence of efficacy in the field is minimal; or vaccines that may produce a relatively higher incidence of adverse events with limited benefit. The Task Force lists the feline infectious peritonitis (FIP) vaccine as not generally recommended. This vaccine is labeled for administration from 16 weeks of age, whereas many kittens become infected with coronaviruses well before this age. It also contains a serotype II strain of FIP virus. Serotype I FIP virus strains predominate in the field and do not have cross-reactive neutralizing epitopes with serotype II strains. Therefore, as noted in the previous iteration of these guidelines,^1,33 there remains insufficient evidence that this vaccine induces clinically relevant protection in the field.

The decision to vaccinate, even with core vaccines, should be based on a risk-benefit assessment for each cat and for each vaccine antigen. Benefits of vaccination should be balanced against the risk of adverse events, likelihood of exposure, and disease severity. Every effort should be made to ensure that cats are healthy before vaccination. However, concurrent illness (including retroviral infections) does not necessarily preclude vaccination.³⁴ The 2020 AAFP Feline Retrovirus Testing and Management Guidelines state that vaccines should not be avoided in cats with retroviral infection because they can develop more severe clinical disease related to FPV and upper respiratory tract infections after natural exposure compared with uninfected cats.³⁴