University of Glasgow, Institute of Comparative Medicine, Faculty of Veterinary Medicine, Bearsden
Glasgow, Scotland, UK
FeLV is declining in prevalence
The decline in the prevalence of feline leukaemia virus (FeLV) in many communities of cats over the last 20 years has been remarkable. Indeed, in some countries FeLV has become quite rare particularly in purebred cats (which perversely has brought the attendant problem of a high proportion of false positive results by in-practice tests). This success has been achieved first by the isolation of carriers of the virus by routine diagnostic testing and latterly in addition by vaccination. The relative contribution of each of these measures to the control of the infection is not clear. Where there is reliance on vaccination as the prime measure against an infection that is almost always fatal, it is obviously helpful to have vaccines that are highly effective.
How good are FeLV vaccines?
The range of immunogens in vaccines for FeLV is uniquely wide and includes inactivated whole virus, inactivated viral 'subunits', recombinant viral protein and live recombinant viral vectors. While several studies have compared some of these products and have indicated that there is a hierarchy of efficacy, the order of this hierarchy has varied in different trials. However, it appears that the highest efficacy achieved is around 80%. Is this level sufficient to maintain a virus-free population? Can higher levels be achieved?
Vaccinologists often state (particularly in applications to fund their research) that to produce effective vaccines a thorough knowledge of the immunogens and the immune mechanisms responsible for protection is necessary. This argument is not entirely convincing as the majority of the, mostly very successful, vaccines used in veterinary practice were developed empirically. However, perhaps a better understanding of these issues may allow us to develop even more effective vaccines and produce vaccines for infections that have been refractory to such control until now.
Rationale in the development of FeLV vaccines
Initially the development of FeLV vaccines followed traditional approaches. We showed that vaccination was feasible using an inactivated virus-infected cell vaccine and subsequently developed the first whole inactivated virus vaccine. We believed that the induction of virus neutralising antibodies, which are prominent in the serum of cats that recover from natural FeLV infection or from experimental challenge following vaccination, was responsible for immunity. Indeed the passive transfer of antibodies protected cats effectively from infection. As the antigen that was the target for neutralising antibodies was known to be the FeLV surface glycoprotein, gp70, we assumed that this component was the effective immunogen in these vaccines. This logic led to the development of a successful 'second generation' vaccine using a pure recombinant version of this protein, produced in bacteria. The only problem with this logic was that none of these vaccines induced neutralising antibodies before challenge. Perhaps other mechanisms were involved in vaccinal immunity? The most recent type of FeLV vaccine to be launched comprises a live canarypox-FeLV recombinant virus that includes not only the FeLV envelope gene, but the other two FeLV genes as well. Perhaps gene products other than gp70 induce immunity? If they do, it is very likely that cell mediated immunity is an important component in protection.
FeLV vaccines work through cell mediated immunity
This suggestion is supported convincingly by the results of our recent experiments on FeLV DNA vaccination. In two experiments, intramuscular inoculation of all three FeLV genes, together with feline interleukin-18 (IL-18) gene as an adjuvant, protected 100% of kittens from challenge. IL-18 strongly enhances the cellular component of the immune response. While no antibody to any FeLV protein was found in the vaccinated cats, strong cytotoxic T cell activity against FeLV-infected cells was evident. These results, and those from our experiments on how cats resist natural infection, provide very strong evidence that cell mediated immunity is the prime protective component of the immune response to FeLV.
These results may also explain how current commercial FeLV vaccines work. Initially it was rather surprising that a non-glycosylated, denatured recombinant envelope protein actually protected cats against FeLV, as it seemed unlikely to be able to induce neutralising antibodies. Now we think we know why it works. Also the rationale of delivering FeLV proteins via a recombinant canarypox virus is sensible, as live viruses induce cell mediated immunity. Whether the most effective vaccine, DNA, will be developed commercially seems unlikely due to the perceived problems of licensing such a novel product. Could this be yet another first for FeLV vaccination?