Feline calicivirus: prophylactic immunisation

Since it is practically impossible to eliminate carriers of feline calicivirus (FCV) from the environment, the control of FCV infection is largely based on vaccination. The fact that caliciviruses can exist in many populations of cats without causing serious clinical problems complicates the prevention of the spread of this infection in nature.

The rhinotracheitis caused by type 1 feline herpesvirus feline herpesvirus-1, FeHV-1) and FCV infections account for more than 90% of upper respiratory tract infections in the cat and are often present concomitantly. The risk of exposure to both viruses is very high, given that both pathogens are widely distributed in the feline population. Consequently, it is good practice to vaccinate all kittens and give a booster vaccination to adult animals. Cats whose history is not known should be considered at risk and vaccinated, planning periodic boosters also for these animals. Kittens are protected by passive immunity received through the colostrum and this can interfere with the efficacy of vaccines before the 12_^th week of life.

Over the last 15 years, prophylactic vaccination against FCV has mainly been performed using vaccines formed of attenuated virus prepared with the F9 strain and administered parenterally. Despite the large scale use of vaccination, FCV is still very widespread and even vaccinated animals can become asymptomatic carriers. In fact, the prevalence of FCV remains high, at about 50% and, among the population of healthy cats that participate in exhibitions in the United Kingdom, about 25% diffuse the virus. (Coutts et al. 1994) In  comparison the prevalence of cats that spread FHV-1 ranges from 1-5% in the population, although it can reach 50% in cat shelters, mostly because of the high percentage of subjects chronically infected by FHV-1 (Pedersen et al. 2004).

The facility with which strains of FCV resistant to vaccines develop in the feline community could indicate both that the serological differences are more important than previously thought and that the immunisation is less effective than predicted. Although vaccines against FCV are effective in decreasing the severity of clinical signs, their inhibitory effect on carriers of the virus is very limited; in fact, caliciviruses can be isolated from the oral cavity of 20-30% of healthy cats in the community or breeding facilities, where vaccination is performed routinely.

All this could be attributed to: (i) the circulation of FCV strains that are very different, from an antigenic point of view, from those of the parent F9 vaccine; (ii) the residual virulence of the attenuated parent vaccine; and (iii) the capacity of the vaccine to confer protection against the disease but not against the infection. Indeed, one often undervalued problem is that calicivirus is able to mutate fairly quickly in the environment, giving rise to new strains which, although partially sensitive to the current vaccines, tend to escape complete control giving rise to new, partially resistant foci of infection. Although the current vaccine strains provide some cross-protection, this protection is not necessarily effective against all the viral isolates.

For this reason, alongside the attenuated live vaccines, there are now inactivated immunising products on the market, including a recently produced bivalent inactivated vaccine prepared with FCV variants different from the F9 strain. This vaccine seems to be able to protect cats from infection with phylogenetically and antigenically very varied isolates of FCV. Most of the vaccines are suitable for routine vaccination programmes and, in previously unexposed cats, most induce a reasonable level of protection against the clinical disease. However, as already described, it should be remembered that vaccination does not protect against infection by either  FCV or FHV-1. Vaccinated animals do, therefore, remain a potential source of field virus for other cats.

While there is a single serotype of FHV-1 and it is, therefore, more probable that vaccines against this virus could protect equally well against all FHV-1 field isolates, the diversity of FCV implies that no single vaccine strain is able to protect equally against all field strains of FCV. This is the reason why a certain number of FCV strains have been selected to be included in the vaccines, on the basis of their being considered to have the greatest cross-reactivity. The new bivalent vaccine therefore includes not only the commonly used strains (FCV F9 and FCV 255), but also two new strains of FCV (FCV 431 and FCV G1) (Poulet et al. 2005).

This is a very interesting fact because, for the first time, pharmaceutical companies are trying to gain a marketing advantage through promoting the greater cross-reactivity of the FCV vaccine strains. The capacity to neutralise a high percentage of field isolates will probably play an ever more important role in the marketing of these vaccines (Pedersen and Hawkins 1995; Lauritzen et al. 1997). It is, therefore, to be hoped that the efficacy of the commercially available vaccines is periodically monitored against representative “panels” of field viruses.

Although vaccination provides good protection against acute oral and respiratory infections, it should be remembered that it does not protect against the infection or eliminate the virus from the environment. Furthermore, no single vaccine strain is able to protect equally well against all strains of FCV.

VACCINE PROTOCOLS

According to the guidelines for the vaccination of cats produced by the Vaccination Guidelines Group (VGG), (Day MJ et al, 2007) a commission of international experts belonging to the World Small Animal Veterinary Association, and by the ABCD [5](European Advisory Board on Cat Diseases), (Radford AD et al, 2009) calicivirus vaccination is considered a basic vaccination.

The vaccination is generally carried out between the 6^th and 12^th weeks of life, ideally at the 9^th week but, because of a possible reduction of the efficacy of the vaccination in this age range as a result of maternal antibodies, it is recommended that periodic boosters are given every 3-4 weeks, until after the 12^th week. If, on the other hand, the first vaccination is performed at 12 weeks or beyond, the recommendation is for a single booster after 3-4 weeks.

The minimum duration of immunity following vaccination is 3 years: consequently, after the first series of vaccines and a first booster after 1 year, 3-yearly boosters are considered protective, in the absence of real situations of risk (free-ranging cats, colonies, breeding facilities).

Most of the commercially available vaccines against FCV are polyvalent vaccines. Their use has never been associated with problems such as the development of inoculation site sarcomas but, since most of them are live attenuated vaccines, their use should be avoided in pregnant cats and kittens less than 4 weeks old. Likewise, they should not be used in adult animals with chronic feline stomatitis, in which FCV seems to be a determinant. In such subjects it is advisable to use vaccines based on genetic engineering or an inactivated valence. In the case of endemic infections where the risk of contagion is very high (e.g. catteries), the vaccine can be administered by the intranasal or conjuctival route already from the age of 2 weeks.

Suggested readings

1. Radford AD, Sommerville L, Ryvar R, et al. Endemic infection of a cat colony with a feline calicivirus closely related to an isolate used in live attenuated vaccines. Vaccine 2001; 19: 4358–62.
2. Gaskell RM, Dawson S, Radford AD. Feline respiratory disease. n: Greene CE, ed. Infectious diseases of the dog and cat. Philadelphia: Saunders Elsevier, 2006: 145–54.
3. Radford AD, Dawson S, Coyne KP, Porter CJ, Gaskell RM. The challenge for the next generation of feline calicivirus vaccines.Vet Microbiol 2006; 117: 14–18.
4. Coutts, A. J., S. Dawson, et al. (1994). Isolation of feline respiratory viruses from clinically healthy cats at UK cat shows. Veterinary Record 135: 555-556.
5. Pedersen, N. C., R. Sato, et al. (2004). Common virus infections in cats, before and after being placed in shelters, with emphasis on feline enteric coronavirs. Journal of Feline Medicine and Surgery 6: 83-88.
6. Poulet, H., S. Brunet, et al. (2005). Immunisation with a combination of two complementary feline calicivirus strains induces a broad cross-protection against heterologous challenges. Vet Microbiol 106(1-2): 17-31.
7. Lauritzen, A., O. Jarrett, et al. (1997). Serological analysis of feline calicivirus isolates from the United States and United Kingdom. Veterinary Microbiology 56: 55-63.
8. Pedersen, N. C. and K. F. Hawkins (1995). Mechanisms of persistence of acute and chronic feline calicivirus infections in the face of vaccination. Veterinary Microbiology 47: 141-156
9. Radford AD, Addie D, Belák S, Boucraut-Baralon C, Egberink H, Frymus T, Gruffydd-Jones T, Hartmann K, Hosie MJ, Lloret A, Lutz H, Marsilio F, Pennisi MG, Thiry E, Truyen U, Horzinek MC. Feline calicivirus infection. ABCD guidelines on prevention and management.J Feline Med Surg. 2009 Jul;11(7):556-64.
10. Day MJ, Horzinek MC, Schultz RD; Vaccination Guidelines Group (VGG) of the World Small Animal Veterinary Association (WSAVA). Guidelines for the vaccination of dogs and cats. Compiled by the Vaccination Guidelines Group (VGG) of the World Small Animal Veterinary Association (WSAVA).  J Small Anim Pract. 2007 Sep;48(9):528-41.