Control of feline leukaemia virus

Abstract

Feline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS (acquired immune deficiency syndrome) in man. FeLV is transmitted among cats by contagion. The main sources of infection are persistently infected carrier cats which continuously excrete virus. Dissemination of FeLV among cats may be prevented by identifying infected carrier cats and removing them from contact with non-infected cats. Removal programmes using indirect immunofluorescence antibody tests were applied successfully in The Netherlands. The proportion of FeLV-positive cats decreased from 9% in 1974 to approximately 3% in 1985 during such a programme. The results of a removal programme carried out in a catbreeders' society were even better: the incidence of cats positive for FeLV decreased from 11% in 1974 to less than 2% within 4 years. None of the cats tested in this society has been found to be positive for FeLV since 1984. Besides removal programmes, other methods of control, such as pre-exposure treatment, were developed to prevent the spread of FeLV. We attempted to protect kittens against oronasal infection with FeLV by treatment with virus-neutralizing (VN) monoclonal antibodies (MoAbs) directed against an epitope on the viral glycoprotein gp70. However, no protection was achieved. It is unlikely that the amount of VN antibodies, the mode and route of their application or the infectious dose of FeLV used can account for this failure. Other possible explanations for the lack of protective effect are that (i) the restricted epitope specificity of the MoAb preparation used may have led to selection of neutralization-resistant virus mutants, or (ii) other mechanisms than virus neutralization (complement-mediated lysis, antibody-dependent cell cytotoxicity), that may be involved in protection, function less efficiently with MoAb. However, in the light of our finding that an early anti-idiotypic response is observed in all cats following administration of the MoAb preparation, the rapid clearance of anti-FeLV MoAb from the circulation is a more likely explanation. Efforts were further made to develop a vaccine for controlling FeLV infection. The immunostimulating complex vaccine (FeLV-ISCOM vaccine), a subunit vaccine in which FeLV gp70 is presented in a particular manner, looks promising. The protective effect of FeLV-ISCOM vaccine was studied by vaccinating six 8-week-old SPF cats with ISCOM, followed by oronasal challenge with FeLV. Six unvaccinated cats were also challenged with the same dose of FeLV. The vaccinated cats developed FeLV serum antibodies, some of which were directed to the shared epitope on gp70. At 10 weeks after challenge, none was viraemic, whereas four of the control cats had developed FeLV viraemia. The potential of FeLV-ISCOM vaccine to induce protective immunity in cats against FeLV was also shown in a field experiment. The generation of an anti-idiotype vaccine was another approach to developing a FeLV vaccine. Virus-neutralizing mouse monoclonal antibodies were generated against an epitope of FeLV gp70. Against one of these, MoAb 3–17, a panel of 15 anti-idiotype monoclonal antibodies (MoAb2) was generated. They recognized partially overlapping private idiotypes within the paratope of MoAb 3–17. Repeated immunization with these MoAb2 coupled to keyhole limpet haemocyanin (KLH) resulted in low-titered anti-FeLV serum titers in BALB/c mice. In a second series of experiments, rabbits were immunized with an affinity-purified polyclonal cat anti-FeLV neutralizing antibody preparation. Immunization of BALB/c mice with Ig from these rabbits resulted in high anti-FeLV antibody titers within 3 weeks.