Vaccines in Small Animals: Feline Vaccination

PRESENTATION

BROCHURE

Vaccines in Small Animals

Feline Vaccination Fernando Fariñas Guerrero (editor) M.ª Luisa Palmero Colado Rafael Astorga Márquez

Vaccines in Small Animals

Feline Vaccination

Vaccines in Small Animals

Fernando Fariñas Guerrero (editor)

Feline Vaccination

M.ª Luisa Palmero Colado Rafael Astorga Márquez

eBook

available

Correct vaccination of cats requires consideration of a broad range of clinical situations and vaccination options, and obliges veterinary surgeons to constantly update their knowledge in order to appropriately deal with the challenges that arise in daily clinical practice.

Using a thoroughly practical approach, this book takes an in-depth look at vaccines and vaccination to provide veterinary professionals with the information they require to address the many doubts and questions that arise in relation to this topic.

TARGET AUDIENCE:

✱ Small animal vets ✱ Veterinary students FORMAT: 22 × 28 cm NUMBER OF PAGES: 136 NUMBER OF IMAGES: 60 BINDING: hardcover

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Authors FERNANDO FARIÑAS EDITOR Expert in the fields of clinical immunology and infectious diseases.

MARÍA LUISA PALMERO Degree in veterinary medicine from the Complutense University of Madrid, Spain. Gattos cat hospital, Madrid.

RAFAEL ASTORGA PhD in veterinary medicine from the University of Murcia, Spain. Full professor of animal health at the University of Córdoba.

KEY FEATURES:

➜ P rovides answers to the most frequent doubts about vaccination in cats. ➜ Includes recommendations about when and how to vaccinate cats depending on the disease and situation. ➜ Review of the current knowledge on infectious diseases and how they are prevented written by renowned experts in the field.

Presentation of the book Vaccinations form an important part of the health plans we prepare for our pets. In veterinary practice, vaccines are our most effective tool in the preventive medicine arsenal, besides constituting a significant source of income. Vets normally follow the administration guidelines indicated by the manufacturer. However, in recent years questions and even doubts have arisen concerning the duration of the immunity conferred by some vaccines and whether annual revaccinations are required. Contrastingly, other specialists believe that current data do not provide conclusive evidence of the immunity periods claimed by the manufacturers. This places vets in a difficult position when it comes to offering advice to their patients’ owners. Vaccination is not always a harmless procedure and each administration must be accompanied by a risk assessment to determine the vaccine strain’s potential for residual virulence and unwanted side effects. The immunogenicity of a vaccine depends on many factors, not least those specific to each animal, including their age, sex, breed, whether they have any underlying diseases, are being administered immunosuppressants, malnourished, stressed, etc. Another point to consider is that in developed countries, with access to veterinary services, there is a relatively high population of immunosuppressed cats and dogs. A large number of pets receive immunosuppressive therapies for multiple diseases, not to mention the long list of animals that undergo major surgery or suffer from chronic illnesses or “immunodysregulatory” infections. This increases the likelihood of primary vaccination failure, with vaccines that prove ineffective or only confer short-lived immunity. There is a current tendency towards a change in practice and mentality by both veterinary surgeons and pet owners in pursuit of greater, better, and more rational immunisation for our pets.

Vaccines in Small Animals Feline Vaccination

Immunisation protocols must therefore undergo a change in policy wherein the pet’s vaccination regime forms part of a complete annual health and well-being revision programme. Vaccinating is a clinical activity that should be performed exclusively by vets after a thorough evaluation of each patient’s specific state of health and characteristics, with the ultimate aim being to decide whether or not to vaccinate and, when necessary, to select the most suitable protocol.

The variety of clinical situations, possibilities, and options available for the vaccination of cats means small animal vets must remain abreast of the latest developments at all times, so they can offer the appropriate solution to any problem that arises in their daily clinical practice. With this in mind, we have decided to publish this book in which the first unit explores the essential knowledge regarding vaccines and vaccinations, followed by a predominantly practical unit which will help veterinary clinicians find answers to the many and often significant doubts that arise when practising feline vaccinology.

hkeita/shutterstock.com

Dr. Fernando FariĂąas Guerrero Editor

Authors Fernando Fariñas Guerrero Fernando Fariñas is a recognised expert in the fields of clinical immunology and infectious diseases, and was based outside of Spain for a large part of his professional career.

He is the founder and president of Fundación IO, an organisation dedicated to developing international projects to combat outbreaks of zoonoses and emerging infectious diseases.

He holds an international diploma in tropical medicine and leprology. His work focuses primarily on the study of zoonotic diseases in the fields of infectious pathology and immunoinfectology, vaccinology, immunonutrition, auto immunity, and immunodeficiencies within the field of clinical immunology.

He is an advisor to various national and international public and private organisations, and a member of specialised study groups including immunotherapy, immunodeficiencies, and vaccinology groups, as well as various working groups focused on vector-borne infectious diseases and zoonoses. He currently coordinates the International Group of Experts on Emerging Infectious Diseases and Zoonoses and the global health group of the One Health Initiative.

He has presented his work at numerous conferences, master’s courses and specialised courses in the fields of clinical immunology, infectious diseases, and vaccinology. He is the author of several books and numerous articles in his field of expertise in both Spanish and international journals.

He currently directs the Institute of Clinical Immunology and Infectious Diseases in Málaga, and serves as president of the Spanish Ynmun Association, which studies immunological and infectious diseases. He has received numerous national and international awards.

Vaccines in Small Animals Feline Vaccination

Marisa Palmero Colado María Luisa Palmero Colado holds a degree in veterinary medicine from the Complutense University of Madrid, Spain. She is a cofounder of and partner at the Gattos Centro Clínico Felino, a hospital for cats in Madrid. In 2016 she was awarded the title of University Specialist in Endoscopy and Minimally Invasive Surgery by the University of Cáceres at the Jesús Usón Minimally Invasive Surgery Centre. She is certified in feline medicine by the Spanish Small Animal Veterinary Association (AVEPA) (2012) and in 2011 earned her General Practitioner Certificate in Feline Practice from the European School of Veterinary Postgraduate Studies. In 2011 she enrolled in the Feline Internal Medicine course at the Centre for Veterinary Education at the University of Sydney. She is a member of the International Society of Feline Medicine, American Association of Feline Practitioners, Madrid Small Animal Veterinary Asssociation, AVEPA, and the scientific committee of GEMFE (AVEPA’s working group of specialists in feline medicine).

She teaches postgraduate students in feline medicine at CEU-UCH University, Valencia, Spain, as well as in Chile and Argentina.

She is coauthor of the book Enfermedades infecciosas felinas (Feline Infectious Diseases) which was published in 2010, and has authored clinical case reports and original articles in Spanish and international internal medicine and feline medicine journals. She has spoken at conferences in Spain and elsewhere and delivered lectures throughout Spain. Her main areas of interest are internal medicine and diagnostic imaging.

Rafael Astorga Márquez Rafael Jesús Astorga Márquez holds a degree in veterinary medicine from the University of Murcia, Spain. He is currently professor of animal health at the University of Córdoba, where he coordinates year 5 of the Preventive Medicine and Health Policy module of the veterinary medicine degree. He has also served as Vice Dean of Students and University Extension (2006–2010) and academic secretary of the Faculty of Veterinary Medicine (2010–2014). He is a corresponding academic of the Royal Academy of Veterinary Sciences of Eastern Andalusia, a diplomate of the European College of Small Ruminant Health and Management (ECSRHM), and a member of the editorial committee of the journal Producción Animal (Animal Production) since 2013.

He is a member of the AGR-256 research group (Animal Health: Disease Diagnosis and Control) of the University of Córdoba. He has authored numerous publications in technical and scientific journals, as well as JCR-indexed scientific journals, and participated in multiple Spanish and international research projects. His main lines of research are infectious diseases of domestic and wild animals, preventive medicine in companion animals, diagnosis and control of animal salmonellosis, animal health and food safety in Iberian pigs, use of essential oils as an alternative to antimicrobials, mastitis in goats, and farm biosecurity. He has been a member of the Spanish Association of Veterinary Specialists in Laboratory Diagnosis (AVEDILA) since 1997, and served as the organisation’s spokesperson from 2004 to 2009.

Table of contents Basic vaccinology 1. Immunological aspects of vaccination 2. Characteristics, types, and composition of vaccines 3. Immunisation failures 4. Introduction to vaccine reactions 5. Frequent doubts about vaccination in small animals

Feline vaccination 6. Vaccination against feline retroviruses 7. Vaccination against feline infectious peritonitis 8. Vaccination against calicivirus 9. Vaccination against herpesviruses 10. Vaccination against panleukopaenia 11. Vaccination against feline chlamydiosis 12. Feline vaccination protocols 13. Vaccine protocols 14. Frequently asked questions about feline vaccination

References and recommended reading

Editorial Servet

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Plaza Antonio Beltrán Martínez, 1 Centro Empresarial El Trovador planta 8, oficina 50002 Zaragoza, Spain

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+34 976 461 480

Vaccines in Small Animals

Feline Vaccination Fernando Fariñas Guerrero (editor) M.ª Luisa Palmero Colado Rafael Astorga Márquez

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VACCINATION AGAINST FELINE RETROVIRUSES

Feline leukaemia virus Description of the pathogen Feline leukaemia virus (FeLV) is a singlestranded RNA virus of the retrovirus family that infects cats worldwide, as well as other felids including the wildcat and the Iberian lynx. Four subtypes are described: A, B, C, and T. Subtype A is the only one with infective capacity.

FeLV is an oncogenic virus that replicates in numerous tissues, giving rise to neoplasms, haematopoietic alterations, immunosuppression, and myelopathies. The clinical picture in FeLV-infected cats varies, depending in part on the predominant viral subtype (Greene, 2008).

Transmission The main route of transmission is contact with the saliva of cats with persistent viraemia, either during grooming or through contact with drinking troughs and feeders. The concentration of virus in saliva is very high, even higher than that found in plasma. The virus can also be transmitted through any bodily fluid (tears, nasal discharge, urine, milk, vaginal fluid, and semen) and transplacentally, although these routes of infection are less efficacious.

Transmission through sneezing or coughing is very unlikely.

In a hospital environment, blood transfusions from untested donor cats should be avoided, since this constitutes an important route of infection (Cattori et al., 2009; GomesKeller et al., 2009).

Pathogenesis FeLV displays tropism for the cells of the haematopoietic system. After contact, it binds to the surface of the target cells. Fusion of the viral envelope with the cell wall results in subsequent release of the nucleocapsid containing the viral RNA. This RNA is transcribed to DNA by reverse transcriptase and the DNA is then transported to the cell nucleus where it is integrated into the host DNA to form the provirus. The integrated DNA produces messenger RNA that encodes capsid proteins as well as RNA that gives rise to new viral particles.

Once assembled, these particles leave the cell by budding. This process does not cause cell death and during mitosis the daughter cells inherit the provirus, allowing retrovirus infections to persist for life (Greene, 2008).

Vaccination against feline retroViruses

There are four possible scenarios following contact with the virus (Hartmann, 2012): 1. Abortive infection: after infection and replication in local lymphatic tissue, mainly lymphocytes and tonsillar macrophages, cats that mount a powerful humoral and cellular response can prevent viral multiplication and dissemination to other parts of the body. Abortive infection occurs after exposure to a low viral load.

2. Progressive infection: occurs in cats with an ineffective immune system. In these cases, the virus spreads through the lymphocytes and monocytes of the blood from the oropharynx to the thymus, spleen, lymph nodes, and salivary glands, where it replicates. After this primary viraemia, the virus invades the bone marrow where it infects haematopoietic precursors, causing lifelong viraemia. The virus is present in the blood, both free and in the form of provirus in cells, and spreads throughout the body replicating on a massive scale. Cats with persistent viraemia are infectious and develop clinical signs.

3. Regressive infection: after primary viraemia an adequate immune response occurs, usually 3–6 weeks after infection, resulting in almost complete elimination of FeLV. However, a small viral population can remain integrated in the cellular DNA of circulating lymphocytes or monocytes in the form of provirus, with minimal replication. This viral population can be detected using more sensitive diagnostic techniques such as quantitative real-time PCR for DNA/RNA.

These cats do not shed virus in their secretions, and are therefore not infectious, but can spread the disease via blood transfusions.

After a regressive infection, the infection can be completely eliminated or potentially reactivated.

4. Atypical or focal infection: this is a rare form of infection characterised by intermittent antigenaemia, and is the result of the presence of the virus not in blood or bone marrow, but in other organs such as the bladder, eyes, and mammary tissue, where it replicates intermittently. This can give rise to mothers who test negative for FeLV, but transmit the infection to their offspring through their milk. On ELISA, atypical infections produce discordant results or alternating negative and positive results.

Clinical signs During the initial viraemia phase clinical signs are nonspecific, and include depression, fever, and anorexia of variable duration depending on the viral load and the cat’s immune status.

Clinical signs can vary considerably during the persistent viraemia phase, and include tumours (mainly lymphoma and leukaemia), serious haematopoietic alterations, and immunosuppression. Other clinical signs include reproductive, neurological, and ocular alterations, and immune-mediated diseases such as glomerulonephritis and immune-mediated anaemia (Figs. 1–7).

Survival time is 2–3 years in 80 % of persistently viraemic cats, but can be higher in cats that do not live in communities.

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2 1

Figure 1. Bilateral nephromegaly caused by a renal lymphoma in a cat positive for FeLV. Figure 2. Ultrasound image of a high-grade lymphoma: loss of normal layered stratification and evident thickening of the jejunum in a FeLV-positive cat.

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b

Figure 3. Marked thickening of the intestine caused by invasion of a high-grade lymphoma in a FeLV-positive cat (a). Section of an intestinal loop (b).

Figure 4. Cytology of a hepatic lymphoma in a cat with feline leukaemia.

Figure 5. Immune-mediated dermatitis and conjunctivitis in a FeLV-positive cat.

Vaccination against feline retroViruses

Figure 6. Petechiae caused by immune-mediated thrombocytopaenia secondary to FeLV infection.

Figure 7. Uveitis in a cat with feline leukaemia.

Diagnosis Diagnosis is established by detection of the p27 viral protein by ELISA (enzyme-linked immunosorbent assay) in serum (antigenaemia), of provirus in blood and bone marrow by DNA-PCR, or of viral RNA in blood and saliva

by RNA-PCR (Hartmann et al., 2007; Torres et al., 2008).

In most cats the ELISA result is positive between 3 and 6 weeks after exposure to the virus.

Although ELISA is widely used, DNA-PCR to detect provirus in blood or bone marrow is a much more sensitive means of demonstrating exposure to FeLV, since cats are positive for provirus 1–2 weeks after infection.

Generally, RNA-PCR is used to analyse saliva samples from infected cats living in communities, and provides a simple means of identifying FeLV-positive cats. The result of this test correlates with that of blood ELISA, and is positive 1 week after exposure to FeLV (i.e. at least 2 weeks before ELISA). It is therefore very useful for testing cats living in shelters and communities.

To avoid false negatives in cats that have potentially been exposed to the virus, a negative first result should always be followed by repeated analyses 3 and 6 weeks later (ELISA) or 1–2 weeks later (PCR) to rule out the possibility that the cat was initially tested during the incubation phase.

If a positive test result is obtained, a subsequent test should always be performed 2 months later to determine whether the infection is regressive or progressive (HoffmanLehmann, 2017).

The following tests can be used to distinguish the different phases of the disease: in abortive infections both PCR and ELISA results are negative; in regressive infections, ELISA results are negative while DNA and RNA PCR are positive, but reveal a low viral load; in progressive infections, both ELISA and PCR results are always positive.

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Immunofluorescence diagnosis detects the presence of p27 protein in infected cells and platelets. This test does not produce a positive result until the bone marrow is infected, which usually occurs 3 weeks or more after viraemia is established. This test is not as diagnostically useful as ELISA or PCR.

Immunity Sensitivity to FeLV infection is higher in young cats, since natural resistance to infection develops as the cat ages. In a study by Grant et al. (1980) 42 kittens and 28 adult cats were exposed to a group of cats of which 30 % were infected with FeLV. After 7 months of exposure, 95 % of the kittens were viraemic, while only 11 % of the adult cats were infected. After 2 years of exposure, the number of infected adult cats increased to 43 %, confirming that continuous exposure to FeLV increases the likelihood of becoming infected.

A later study (Wilson et al., 2012) corroborated the existence of natural resistance to infection, demonstrating that the immune system of 10-month old cats offers greater protection against FeLV than that of younger cats. Vaccinated cats were compared with an unvaccinated control group and immunity was assessed 8, 20, and 36 months after intraperitoneal inoculation of the virus. For all groups, a corresponding control group of 4-month-old kittens was exposed to the virus. The results

showed that 100 % of unvaccinated kittens were viraemic. By contrast, after exposure of 10-month-old unvaccinated cats only 36 % were found to be persistently viraemic.

Therefore, the immune system of 10-month-old cats responds more competently to FeLV infection than that of kittens.

Finally, a recent study (Fontaine et al., 2016) reported that 56 % of unvaccinated cats that were intraperitoneally inoculated with FeLV virus at 3 years of age did not develop persistent viraemia, again demonstrating that adult cats develop natural resistance to feline leukaemia.

Within communities, the risk of infection of an unvaccinated adult cat living with a persistently viraemic cat is estimated at approximately 10–15 % (Hartmann, 2007).

Prevention

Environmental hygiene measures The most effective means of decreasing the spread of the virus is to isolate infected cats.

However, the risk of infection by fomites is very low; retroviruses have an envelope that makes them especially fragile in the environment, and are usually rapidly inactivated by standard disinfectants. They can only survive outside the host for a few minutes owing to their sensitivity to heat and dryness.

If viraemic cats cannot be isolated, all cats living with them should be vaccinated in order to enhance their natural immunity.

Vaccination against feline retroViruses

Vaccination against FeLV According to WSAVA guidelines, vaccination against feline leukaemia is optional, not compulsory. However, this view is somewhat controversial given that FeLV infection is still very prevalent in certain parts of the world.

Therefore, the decision to vaccinate should be based on the animal’s risk of future exposure (Day et al., 2016).

What types of vaccines are commercially available?

There are several commercially available vaccines designed for parenteral administration: ■ Inactivated whole-virus vaccine, adjuvanted ■ Inactivated subunit vaccine, adjuvanted ■ Recombinant canarypox virus vaccine, nonadjuvanted According to WSAVA recommendations, nonadjuvanted vaccines should be used whenever possible.

Are recombinant vaccines safe?

The recombinant vaccine uses a nonpathogenic virus (a canarypox virus vector) in which FeLV antigens are transported, obviating the need for adjuvants. Because the canarypox virus is unable to replicate and cause disease in nonavian tissues, the vaccine can be considered safe.

Do vaccines block viral integration and provirus formation?

PCR diagnosis has shown that vaccines may not block the integration of FeLV proviral DNA or prevent minimal viral replication after exposure, but do protect against persistent viraemia

and the development of disease. Cats in which the latter occurs will become latent carriers (Hoffman-Lehmann, 2007).

The biological importance of the integration of proviral DNA in vaccinated cats is unknown.

It may be important to maintain protective immunity by ensuring the expression of viral antigens at very low levels. On the other hand, the integration of viral DNA can give rise to tumours or other FeLV-associated diseases.

Moreover, reactivation of a latent infection can occur, as described in some cats that are positive for provirus and negative for FeLV antigen.

Are some vaccines more effective than others?

Vaccine efficacy is a controversial topic, since in many studies the route of viral inoculation does not resemble natural infection. Interpretation of results is also complicated by the fact that cats develop natural resistance to the disease from 10 months of age. Furthermore, the majority of vaccine studies were carried out before the development of much more sensitive molecular diagnostic techniques, such as PCR, which can confirm latent infections in vaccinated cats after exposure.

Another factor that hinders the interpretation of the efficacy of different vaccines is the sensitivity of the PCR technique used, which may alter the percentage of latent carriers of the virus.

Taking these factors into account, it has been found that all commercially available FeLV vaccines are comparably effective in terms of their ability to prevent

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integration of FeLV proviral DNA after exposure.

This observation is based on the findings of three studies: ■ The first study (Patel et al., 2014), compared the efficacy of two vaccines, an inactivated whole-virus vaccine and a recombinant canarypox virus vaccine, after exposure to FeLV of cats that had received primary vaccination at 8 and 11 weeks of age. The virus was inoculated 3 months after administration of the second vaccine dose. The development of persistent viraemia was evaluated by ELISA and the presence of viral integration by DNA-PCR 3 and 9 weeks after exposure. None of the cats that received the inactivated whole-virus vaccine developed viraemia, and only 9 % carried an integrated virus in the form of a provirus. By contrast, 50 % of the cats that received the recombinant vaccine developed viraemia after exposure and 60 % carried an integrated virus in the form of a provirus, indicating poorer efficacy of the recombinant vaccine. The results of this study are somehat controversial, since the cats were treated with immunosuppressive doses of methylprednisolone acetate (10 mg/kg) on the day of inoculation and 1 week later, thereby suppressing cellular immunity and promoting humoral immunity.

■ The second study (Torres et al., 2010) compared the efficacy of two adjuvanted inactivated whole-virus vaccines. Four months after receiving a booster shot at 35 weeks of age, all cats were intraperitoneally injected with a virulent FeLV strain.

Next, viraemia and the presence of provirus were evaluated weekly by ELISA and PCR,

■

respectively. Of the 8 cats that received the inactivated whole-virus vaccine, antigenaemia and viraemia were absent in 7 and 6, respectively.

A more recent study (Grosenbaug et al., 2017) compared the efficacy of three adjuvanted, canarypox virus–vectored FeLV vaccines with a placebo, under conditions that mimicked natural FeLV infection. Three weeks after primary vaccination 80 kittens were exposed to a virulent FeLV strain. Antigenaemia and the presence of provirus were evaluated weekly for 15 weeks by ELISA and quantitative PCR, respectively. The prevented fractions for each of the vaccines were 93 %, 93 %, and 80 %, respectively, demonstrating that under identical conditions of exposure all three vaccines showed comparable efficacy.

Does vaccination affect the results of diagnostic tests?

No, vaccination does not produce a positive result in either ELISA or PCR tests.

What is the protocol for vaccination in kittens?

In areas in which feline leukaemia remains endemic, all cats of less than 1 year of age should be vaccinated with two doses, beginning vaccination at 8 weeks of age and revaccinating 3–4 weeks later. A booster shot should be administered 1 year later (Day et al., 2016).

Unlike other vaccines, the efficacy of a single dose of the FeLV vaccine has not been determined. Therefore, the value of FeLV vaccination administered as a single dose, as occurs in trap– neuter–return programmes, is questionable.

Vaccination against feline retroViruses

How often should cats be revaccinated for FeLV?

What is the vaccination protocol for low-risk cats?

According to WSAVA guidelines, revaccination of high-risk cats should be performed every 2–3 years. Cats with low risk of exposure to FeLV should not be vaccinated.

This recommendation is supported by the findings of a recent study (Fontaine et al., 2016), which examined whether a vaccine containing purified p45 antigen from the FeLV envelope (together with feline calicivirus, feline rhinotracheitis virus, and live attenuated feline panleukopaenia virus) offered adequate immunity against intraperitoneal inoculation of FeLV 3 years after primary vaccination. Vaccinated cats were compared with a group of unvaccinated control cats. Of the cats vaccinated 3 years prior, 6 % developed persistent viraemia after exposure and 86 % did not, indicating a prolonged duration of immunity.

FeLV survives in the external environment for only a few minutes, and thus transmission via fomites is ineffective. Therefore, vaccination of low-risk cats is not required (Day et al., 2016).

Which is more important, vaccinating kittens or vaccinating cats of over 10 months of age?

The development of natural resistance to FeLV infection with age has been proven: cats of 10 months of age show a more robust immune response to FeLV than younger kittens. Therefore, vaccination of kittens is essential. However, it is inadvisable to exclude adult cats with a high risk of exposure from vaccination programmes, since the risk of developing persistent viraemia is 7 times higher in unvaccinated versus vaccinated adult cats (Fontaine et al., 2016; Wilson et al., 2012).

What is the vaccination protocol for cat communities?

Due to the development of natural resistance to FeLV infection with age, the current recommendation for community cats is to vaccinate every 2 or 3 years (Day et al., 2016).

What is the vaccination protocol for cats of unknown vaccination status?

Cats of unknown vaccination status should be vaccinated, revaccinated 3–4 weeks later, and subsequently revaccinated according to their lifestyle: low-risk cats require no further doses, while high-risk cats should be revaccinated every 2–3 years.

What happens if a FeLVpositive cat is vaccinated without prior knowledge of its disease?

Vaccination of cats that have a latent or regressive infection or are persistently viraemic does not increase the risk of a vaccine reaction or exacerbate the clinical picture.

Moreover, vaccination of a cat infected with FeLV has neither negative nor positive effects on disease progression.

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Feline immunodeficiency virus Description of the pathogen Feline immunodeficiency virus (FIV) is a retrovirus of the genus Lentivirus that is distributed worldwide and causes progressive deterioration of the immune system. Its prevalence is highly variable, ranging from 1 % to 31 % depending on geographical area, and is highest in stray cats (Levy et al., 2008).

Five viral subtypes are described based on their respective nucleotide sequences (A, B, C, D, and E), which confer marked genetic differences, hindering the development of adequate vaccines. Although the most frequently isolated subtypes are A and B, a specific geographic distribution of the virus is described: subtype B predominates in Spain, Portugal and Italy; subtype A is the only subtype found in the United Kingdom; and subtypes A and B coexist throughout the rest of Europe. Subtypes C, D, and E are less common. For example, subtype D has been isolated only in Japan (Horzinek et al., 2008; Greene, 2008).

Transmission The main route of transmission is through inoculation of the virus by biting. For this reason prevalence is higher in stray cats and those with outdoor access (Fig. 8). Therefore, the risk of transmission within stable groups of cats is low provided that fighting is minimal.

Transmission via contact with the vaginal, rectal, or oral mucosa is minimal, but has been demonstrated in experimental conditions (Greene, 2008).

Maternal transmission during pregnancy or lactation is possible, although the proportion of infected kittens depends on the viral load of the mother. Thus, if a cat becomes acutely infected during pregnancy or lactation, up to 70 % of the litter will become infected, while in cats with lower viral loads during pregnancy the entire litter may remain unaffected (O’Neil et al., 1995).

Blood transfusion constitutes another possible route of transmission. Transmission by fomites is unlikely; after a few minutes outside the host the virus loses its infectivity due to its sensitivity to heat, humidity, and ultraviolet light (Hosie et al., 2009).

Pathogenesis Inoculation of the virus results in initial acute viraemia lasting 8–12 weeks. During this period FIV replicates in CD4+ T cells, macrophages, and dendritic cells. Mild clinical signs develop during this phase.

Vaccination against feline retroViruses

After the development of cellular and humoral immunity, the viral load begins to decline, giving rise to a prolonged asymptomatic stage that can last between several months and years. However, during this phase the immune system undergoes profound alterations, and CD4+ T cell levels progressively decrease. This decrease, together with alterations in monocyte, macrophage, neutrophil, and lymphocyte functionality, gives rise to an acquired immunodeficiency syndrome similar to that produced by the human immunodeficiency virus (HIV).

Cats are infectious during all phases of the disease, i.e. the initial viraemia phase, the subclinical phase, and the immunodeficiency phase.

Clinical signs During the initial viraemia period mild clinical signs may be observed, including decreased appetite, fever, and lymphadenopathy lasting approximately 2 weeks. During the subclinical phase of the disease cats can remain asymptomatic for months, years, or even their entire lives. The clinical phase of immunodeficiency is characterised by the development of secondary infections, neurological disease, immune-mediated disease, and tumours, the most common of which is lymphoma.

Diagnosis Diagnosis is usually established by measuring blood antibody levels by ELISA. This should be done about 2 months after contracting the disease, since antibodies may not reach detectable levels until about 60 days after exposure.

Figure 8. The risk of feline immunodeficiency is higher in cats with outdoor access (Bear Fruit Design, Shutterstock.com).

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A positive ELISA result in cats of less than 6 months of age may not indicate infection, but may constitute a false positive result due to the detection of maternal antibodies. In kittens born to infected mothers maternal antibodies may be present in the blood until 6 months of age, although in most cases antibody concentrations decrease to undetectable levels by 4 months of age. For this reason, a second ELISA test should always be carried out after the cat reaches 6 months of age.

Upon detecting antibodies ELISA tests were previously considered unable to differentiate between infected and vaccinated cats. However, two commercially available rapid antibody detection tests have been recently shown to differentiate between the two states with 100 % sensitivity (both tests) and 98 % and 100 % specificity, respectively. By contrast, another available test was unable to distinguish infected from vaccinated cats, and therefore should not be used in cats that have been previously vaccinated (Westman et al., 2015).

A later study found that these tests could produce positive results if performed within 6 months of vaccination, and thus recommended limiting their diagnostic use to between 6 months and 7 years after primary vaccination (Westman et al., 2017).

Another diagnostic option is to perform PCR tests to detect provirus DNA. PCR can reveal, without having to wait until 6 months of age, whether a seropositive kitten is truly infected or whether the result constitutes a false positive caused by the persistence of maternal antibodies. However, the sensitivity and specificity of this test can be low in cases in which the infection is caused by a subtype not identified by PCR.

Treatment Supportive treatment of cats in the immunodeficiency phase depends on the type of disease that develops (immune-mediated, neoplastic, bacterial, etc.). Antivirals, which are registered for the treatment of HIV, can be used but are of variable efficacy and can be highly toxic. To date, no studies have demonstrated the efficacy of immunomodulators such as feline interferon ω (Horzinek et al., 2008).

Immunity The degree to which passive immunity to natural infection is transmitted via colostrum from vaccinated or FIV-infected female cats is unknown.

Antibodies appear between 2 and 4 weeks after natural infection, just after initial viraemia peaks. However, if the initial FIV viral load is very low antibodies may not appear until several months or even 1 year after entry of the virus.

In FIV infections, antibody levels remain more or less constant for long periods of time, even years, decreasing during the final stages of infection. This decrease

Vaccination against feline retroViruses

coincides with a marked decrease in the CD4+:CD8+ ratio, accompanied of a new increase in viraemia and the development of immunodeficiency syndrome (Horzinek et al., 2008).

Prevention

Environmental hygiene measures The ability of FIV to contaminate the environment is very low, since the virus survives only for a few minutes outside the host due to its sensitivity to light and heat.

FIV is also inactivated by any disinfectant, and even by soap (Levy et al., 2008).

Vaccination against FIV Vaccination against FIV is considered noncompulsory according to WSAVA vaccination guidelines (Day et al., 2016), since its efficacy against all circulating virus subtypes in different geographical areas remains unclear (Bęczkowski et al., 2015; Pu et al., 2005). However, the distribution of FIV appears to be increasing and therefore vaccination of high-risk cat populations may be beneficial. Consequently, the recently published WSAVA recommendations classify FIV vaccination, which was formerly not recommended, as noncompulsory.

What FIV vaccines are currently available?

An inactivated vaccine has been commercially available in the United States since 2002 and in Australia since 2004. Five FIV subtypes are described based on their respective nucleotide sequences (A, B, C, D, and E). Commercial vaccines contain only two of the virus subtypes: A and D. As discussed above, these viral subtypes have a specific geographic distribution: subtype B predominates in Spain, Portugal and Italy; subtype A is the only subtype found in the United Kingdom; and subtypes A and B coexist throughout the rest of Europe (Horzinek et al., 2008; Greene, 2008).

How effective is it?

Does it protect against all FIV subtypes?

The vaccine was shown to be effective against subtype A, against exposure to cats infected with subtype B, and against intravenous exposure to subtype B (the most frequently isolated subtype in the United States), since the results of DNAPCR analyses and ELISA tests for all vaccinated cats were negative (Kusuhara et al., 2005).

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However, it only confers a limited degree of cross-protection against other circulating subtypes that may be present in other geographical regions, meaning that cats that receive the FIV vaccine can be infected by these other subtypes (Kusuhara et al., 2005). For this reason it is not commercially available in all countries.

What is the duration of immunity?

Immunity has been quantified in cats exposed to subtype B 12 months after primary vaccination with 3 doses separated by 3-week intervals. Cats were intravenously inoculated with the virus and PCR testing used to determine the CD4+:CD8+ ratio in peripheral blood and lymphatic organs. Ten of the 14Â cats that were vaccinated and exposed to subtype B did not develop infection, whereas all unvaccinated control cats (5) did. The authors concluded that vaccinated animals have adequate immunity against subtype B 12 months after vaccination (Huang et al., 2010).

Can vaccine-induced antibodies be distinguished from those induced by infection?

For many years vaccination was not recommended since there was no way to differentiate between vaccine-induced antibodies and those induced by infection, complicating diagnosis. However, a recent study demonstrated that vaccineinduced antibodies do not interfere with diagnosis using certain commercially available antibody detection tests, provided the test is performed between 6Â months and 7 years after primary vaccination (Westman et al., 2017).

Therefore, at the moment of revaccination these tests can be used to detect possible cases of FIV infection in vaccinated cats that have been exposed to the virus, since the vaccine does not confer complete immunity against all FIV subtypes.

What is the recommended vaccination protocol?

The FIV vaccination schedule requires administration of three doses separated by 3- to 4-week intervals, beginning at 8 weeks of age. After primary vaccination, community cats and all cats with uncontrolled outdoor access should be revaccinated annually.

Does the vaccine have side effects?

In a study of 689 cats that received 2,051 doses, side effects were observed in less than 1Â % (Levy et al., 2008). The vaccine can therefore be considered safe.

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