These studies, which were conducted according to the requirements defined in European Pharmacopeia 5.0, Monograph 01/2005:1321 regarding Feline Leukaemia Vaccine (Inactivated), evaluated protection against a FeLV challenge provided by Versifel FeLV over an extended period. Animals were slightly younger than the target age when first vaccinated with Versifel FeLV (between seven and eight weeks of age) and were challenged with virulent FeLV either eight months, 20
months or 36
months after the vaccination course. Thus, at the time of FeLV challenge, cats in the adult groups were aged approximately 10
months or 38
months old, while the kitten groups were approximately three to four months old. The monograph specifies that for a successful challenge study, the challenge virus must be an epidemiologically relevant isolate, and that less than 20% of vaccinated cats should develop persistent infection and more than 80% of control cats must develop persistent infection.
When referring to the monograph requirements none of the three studies was a complete success, even though they all used the same vaccine. The vaccinated groups did not show persistent antigenaemia and thus it could be considered that the vaccine offered full protection against a subsequent challenge with virulent FeLV during the timescale of each study. This observation is offset by the fact that the adult control animals in each study did not succumb to the challenge infection in sufficient numbers with a maximum of 45.5% animals in the 20
month duration study showing persistent antigenaemia. Given that the FeLV challenge was administered to these cats when they were approximately 10 to 39
months of age, it is likely that some degree of age related immunity to FeLV infection may have been a factor in this low rate of persistent p27 antigenaemia in unvaccinated cats. Age related resistance to FeLV challenge has been reported previously [4
] and consequently this result was not unexpected. Indeed, one study by Hoover and others [10
] showed a rapid decrease in susceptibility to experimental infection with FeLV, with 100% of newborn kittens able to be infected compared to 15% of cats aged 4
months or 1
year old. A recent study comparing FeLV vaccine efficacy challenged cats with a considerably smaller dose volume and titre and achieved persistent antigenaemia in seven of eight controls, as well as five of eight vaccinated cats at seven months of age [11
]. The high rate of p27 antigenaemia observed in the additional kitten control groups, which were approximately 12 to 16
weeks of age when subjected to the same FeLV challenge as the older cats and at the same time, provides evidence that the chosen dose and route of administration for the FeLV material resulted in an effective and aggressive challenge.
The anomalous gp70 antibody result seen in two cats in treatment group T07 on study day 1136 may raise the question of whether the cats might have been exposed to extraneous FeLV during the post vaccination period. This is considered to be extremely unlikely as these observations were only made in a minority of the cats and similar results were observed in group T08 (two vaccinates which had until day 1136 either remained seronegative or had been seropositive on just one occasion post vaccination). Furthermore, all cats in groups T07 and T08 remained healthy throughout the pre-challenge period and were confirmed to be negative for p27 antigen when tested at various intervals prior to challenge. The cats were obtained from a Specified Pathogen Free (SPF) facility and were housed in a bio-security category 2 facility throughout the duration of the study; it would therefore be extremely unlikely that extraneous FeLV virus could have gained access into the facility.
Products of the viral envelope gene, and specifically the major envelope protein gp70, are thought to be involved in virus host range recognition functions, and as such are also major targets for antibody-mediated virus neutralisation [12
]. However, antibodies against gp70 are generally not induced following vaccination [7
], an observation which appears to correlate with findings seen in this study. This suggests that beside antibody seroconversion additional immunological factors (such as cell-mediated immunity) should be considered in the vaccine-induced duration of immunity against FeLV. Indeed, other studies have shown a role for cell-mediated immunity in protection against FeLV. Flynn and others [13
] showed that following vaccination of cats with a FeLV DNA vaccine containing the gag
genes from the FeLV Glasgow A strain there was a higher level of virus-specific effector cytotoxic T lymphocytes in the peripheral blood and lymphoid organs than observed in unvaccinated control, persistently viraemic cats. The apparent absence of viraemia in cats following vaccination with the Versifel FeLV vaccine, in that FeLV antigen could not be detected in serum samples following challenge, does not mean that infection was prevented as clinical observations showed enlarged lymph nodes indicative of FeLV-related disease. Other studies have shown that during an asymptomatic phase of infection that no severe clinical signs were observed, with some cats showing mild stomatitis or gingivitis, diarrhoea and mild weight loss [14
], which is similar to what was observed in the current study. The correlation of protection with low level virus neutralising gp70 antibodies only seen in a small number of vaccinated cats is an observation which has been reported previously. A recent study [11
] examined the immunity to FeLV induced by vaccination with a variety of inactivated viruses. Two of the vaccines were found to protect against subsequent challenge, but this effective containment of the virus occurred despite minimal detectable virus neutralising antibodies being seen.