A vector expressing feline mature IL-18 fused to IL-1β antagonist protein signal sequence is an effective adjuvant to a DNA vaccine for feline leukaemia virus

Abstract

DNA vaccination using vectors expressing the gag/pol and env genes of feline leukaemia virus (FeLV) and plasmids encoding feline interleukin-12 (IL-12) and IL-18 completely protected cats from viraemia following challenge [Hanlon L, Argyle D, Bain D, Nicolson L, Dunham S, Golder MC, et al. Feline leukaemia virus DNA vaccine efficacy is enhanced by coadministration with interleukin-12 (IL-12) and IL-18 expression vectors. J Virol 2001;75:8424-33]. However, the relative contribution of each cytokine gene towards protection is unknown. This study aimed to resolve this issue. IL-12 and IL-18 constructs were modified to ensure effective expression, and bioactivity was demonstrated using specific assays. Kittens were immunised intramuscularly with FeLV DNA and various cytokine constructs. Together with control kittens, these were challenged oronasally with FeLV and monitored for 15 weeks. All six kittens given FeLV, IL-12 and IL-18 were protected from the establishment of persistent viraemia and four from latent infection. Of six kittens immunised with FeLV DNA and IL-18, all were protected from viraemia and five from latent infection. In contrast, three of five kittens given FeLV DNA and IL-12 became persistently viraemic. Therefore, the adjuvant effect on the FeLV DNA vaccine appears to reside in the expression of IL-18.

A Targeted Mutation within the Feline Leukemia Virus (FeLV) Envelope Protein Immunosuppressive Domain To Improve a Canarypox Virus-Vectored FeLV Vaccine

“…Innate immunity probably plays an important role, as suggested by abortive infections in naive cats and some in vitro studies (21). In vaccinated cats, several studies have shown that protection against persistent antigenemia can be obtained in the absence of neutralizing antibodies (22)(23)(24), suggesting a key role for vaccine-induced cellmediated immune responses (25). However, like other retroviruses, FeLV has developed mechanisms to interfere with the host immune response and establish persistent infection.…”

Efficacy of Recombinant Canine Distemper Virus Expressing Leishmania Antigen against Leishmania Challenge in Dogs

“…However, it has recently been reported that IL-18 also augments the IFN-γ-inducing capacity of vaccines, independently of IL-12 [ 42 ]. IL-18 has also been tested as a vaccine adjuvant, and enhanced the efficiencies of various vaccines in mammals [ 43 – 46 ]. Recently, we generated a rCDV that secretes bioactive canine IL-18 and induces IFN-γ production by canine peripheral blood mononuclear cells [ 47 ].…”

Enhancement of Helicobacter pylori outer inflammatory protein DNA vaccine efficacy by co‐delivery of interleukin‐2 and B subunit heat‐labile toxin gene encoded plasmids

“…However, they have practical potential as carrier molecules, having shown less toxicity in both experimental animals and human immunization (29)(30)(31). Research has also shown that co-administration of cytokine proteins or cytokine gene-encoded plasmids enhances comprehensive humoral and cellular immune responses (32)(33)(34)(35). Recently, synthetic CpGs, which prime a Th1 immune response and have shown some encouraging results in H. pylori vaccines, have been approved for use as adjuvants in humans (21,23,(36)(37)(38).…”