A vector expressing feline mature IL-18 fused to IL-1beta antagonist protein signal sequence is an effective adjuvant to a DNA vaccine for feline leukaemia virus.
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.
O'Donovan
Lucy H
LH
MacRobert Laboratories, Institute of Comparative Medicine, University of Glasgow, Bearsden, Glasgow G61 1QH, UK. L.ODonovan@bio.gla.ac.uk
McMonagle
Elizabeth L
EL
Taylor
Samantha
S
Bain
Derek
D
Pacitti
Angela M
AM
Golder
Mathew C
MC
McDonald
Michael
M
Hanlon
Linda
L
Onions
David E
DE
Argyle
David J
DJ
Jarrett
Oswald
O
Nicolson
Lesley
L
D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000235:genetics; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001853:Bone Marrow / Q000821:virology; D002371:Cat Diseases / Q000517:prevention & control* / Q000821:virology; D002415:Cats; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D007375:Interleukin-1 / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D020382:Interleukin-18 / Q000235:genetics / Q000276:immunology*; D005256:Leukemia Virus, Feline / Q000276:immunology*; D021382:Protein Sorting Signals / Q000235:genetics; D011993:Recombinant Fusion Proteins; D012192:Retroviridae Infections / Q000517:prevention & control / Q000662:veterinary; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D014412:Tumor Virus Infections / Q000517:prevention & control / Q000662:veterinary; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D007375:Interleukin-1; D020382:Interleukin-18; D021382:Protein Sorting Signals; D011993:Recombinant Fusion Proteins; D015682:Retroviridae Proteins, Oncogenic; D019444:Vaccines, DNA; D014765:Viral Vaccines; C045569:feline leukemia virus vaccine; D018664:Interleukin-12