Vaccination against FIP and FIV: is it possible?
By Pr. Oswald Jarrett, University of Glasgow, 2007.
(Reprinted with permission).
FIP is a fatal disease caused by infection with feline coronavirus (FCoV). Although the virus is very common in domestic cats, particularly in multi-cat households, most infected cats remain healthy and the disease occurs only in a small proportion of infected animals. However, FIP is now probably the most common infectious cause of death in cats.
FCoV is an extremely contagious enteric virus and is spread by the faecal-oral route. Following exposure to the virus, there are three potential outcomes:
- ~10% of cats become persistently infected,
- ~85% of cats become transiently infected, or
- ~5% of cats are resistant to infection
Infected cats shed virus in the faeces. Cats that have a transient infection recover after many weeks and stop shedding virus, but subsequently they may become re-infected and shed virus again. Cats become seropositive when they are shedding but become seronegative some time after they stop excreting virus. The vast majority of seronegative cats do not shed virus.
How does FCoV cause FIP?
The vast majority of cats that become infected with FCoV are perfectly healthy and do not develop FIP. Rather surprisingly, FIP does not appear to occur in those cats that are persistently infected with the virus. Most cases occur following the initial infection of kittens. This is consistent with the observation that most cases are found in cats less than 12 months of age. Kittens become infected when they are a few weeks old. It has been suggested that the stress of re-homing kittens may contribute to the pathogenesis of FIP. Cats that develop FIP have very much higher amounts of virus in the body than healthy, infected cats. It is likely that this extensive virus replication allows the emergence of the mutant viruses that are associated with the pathogenesis of FIP. These mutant FCoVs are often called 'feline infectious peritonitis viruses' (FIPVs). Another peak of FIP occurs in old cats, which may be due to an increase in virus load because of the waning immune response of older animals. FIP is caused by an extreme inflammatory reaction to the virus which occurs around the walls of blood vessels and leads to the passage of fluid through the vessels into the abdomen ('wet' FIP) or damage to organs, such as the kidney, due to the destruction of essential tissue ('dry' FIP).
How effective is the FIP vaccine that is available in some countries?
Clearly, a vaccine that prevents FIP would be of great benefit to cat welfare. A vaccine has been developed against FIP (Primucell, Pfizer Animal Health). This is an attenuated, temperature-sensitive FCoV that is given by intranasal administration. The virus is able to replicate in cells in the cooler temperatures of the nasal tract but not within the body, which is at a higher temperature. Protection is achieved because the vaccine induces mucosal immunity that extends to the intestine. Kittens should be vaccinated when they are over 16 weeks of age, with two doses, 3-4 weeks apart.
What are the potential problems with this vaccine?
Does the vaccine cause enhanced disease upon challenge? There is a myth that vaccination causes enhancement of FIP, as has been observed in laboratory experiments. This phenomenon is only produced when cats are vaccinated and then challenged with very virulent, FIP-causing, FCoVs. There is no evidence that the current vaccine causes enhancement when vaccinated pet cats are exposed to the types, or dose, of FCoV that occur in nature.
Is the vaccine effective in the field? Several trials of the vaccine have been carried out to find if the vaccine prevents FIP under natural conditions in pet cats. In one study in Switzerland, it was found that the vaccine protected cats, but only if it was administered before the cats became infected with FCoV; the vaccine did not protect cats that were infected before vaccination. This is a problem because most kittens become infected, often from their mothers, long before 16 weeks of age, which is the age at which the vaccine can be given.
The future: can a more effective vaccine be produced?
As indicated by the results of the Swiss research, the main problem with FCoV vaccination is that many kittens become infected before they are able to be vaccinated. Around one-third of infected mothers infect their kittens within 12 weeks of birth. Therefore, a successful vaccine would have to be safe to give to very young kittens and would have to induce immunity in the face of maternally-derived antibodies. An alternative approach would be to vaccinate pregnant cats in order to provide a greater level of passive protection for their kittens during their first few weeks of life, before they could be actively immunised.
The main problems of vaccination
- A vaccine has to be very powerful in order to prevent the infecting FIV from invading cells and establishing a persistent infection
- FIV occurs in several subtypes. If these subtypes are also different antigenic types, a vaccine would have to protect against the predominant subtype in a particular geographic area.
- The current vaccine interferes with diagnosis.
Pathogenesis of FIV
FIV is a common infection in domestic cats throughout the world, infecting about 5% of cats in European countries. The virus is transmitted by biting, and there is no age resistance to infection. Therefore, cats at highest risk of being found to be infected are old, male, free-ranging cats.
The virus infects lymphocytes in which it establishes a persistent infection. An immune response develops that includes both cell-mediated and humoral immunity, which keeps the virus under control for long periods of time. Once infected, cats do not recover from FIV infection because the virus lies dormant within certain cells where it is hidden from the immune response. Many FIV-infected cats live healthy lives but some develop immunodeficiency and eventually die of a variety of clinical syndromes.
The hope for a vaccine is that an immune response can be induced which prevents cells being infected following the entry of virus into the body.
How effective is the FIV vaccine that is available in some countries?
A vaccine, Fel-O-Vax FIV (Fort Dodge) is available in the USA and some other countries. This vaccine consists of inactivated FIV and FIV-infected cells of subtypes A and D, and has been shown to protect cats from experimental challenge with FIV of subtypes A and B, the most common subtypes in North America. The vaccine is administered by injection to cats older than 8 weeks of age in three doses, 2-3 weeks apart.
What are the potential problems with this vaccine?
Does the vaccine protect cats from field virus? Although the vaccine has been shown to protect against laboratory strains of virus, it is not clear if it protects against FIV strains that are present in the field, which may be of higher virulence.
The vaccine interferes with diagnosis. Vaccinated cats have antibodies to FIV which are detected in the common diagnostic tests. Therefore, it is impossible to distinguish vaccinated and infected cats in this way.
The future: can more effective vaccines be produced?
This is not yet clear. A great deal of research is being done by research laboratories and other pharmaceutical companies to produce FIV vaccines. The primary aim is to develop a vaccine that induces both strong cell-mediated and humoral immunity in order to prevent the establishment of a persistent infection, which, as for HIV, is difficult to achieve. If elimination of the virus cannot be achieved, a vaccine that reduced the virus load in a subsequently infected cat might still be very useful because it might reduce the risk of further transmission of the virus, and the development of disease in the infected cat.
In future it will be important to carry out FIV vaccine trials to try to protect against natural infection. In addition, new methods of diagnosis will have to be developed so that vaccinated and infected cats can be distinguished.