title: Protection against feline immunodeficiency virus using replication defective proviral DNA vaccines with feline interleukin-12 and -18.
abstract: A molecular clone of the Glasgow-8 isolate of FIV (FIVGL8) was rendered replication defective by an in-frame deletion in either reverse transcriptase (deltaRT) or integrase (deltaIN) genes for use as DNA vaccines. To test the ability of these multi-gene vaccines to protect against two feline immunodeficiency virus (FIV) isolates of differing virulence, cats were immunized using either DNA vaccine alone or co-administered with interleukin-12 (IL-12) and/or interleukin-18 (IL-18) cytokine DNA. Animals were challenged sequentially with FIV-Petaluma (FIVPET) an FIV isolate of relatively low virulence and subsequently with the more virulent FIVGL8. A proportion of vaccinates (5/18 deltaIN and 2/12 deltaRT) were protected against primary challenge with FIV(PET). Five of the vaccinated-protected cats were re-challenged with FIV(PET); four (all deltaIN) remained free of viraemia whilst all naive controls became viraemic. Following subsequent challenge with the more virulent FIVGL8 these four vaccinated-protected animals all became viraemic but showed lower proviral loads than naive cats. This study suggests that while our current DNA vaccines may not produce sterilizing immunity against more virulent isolates of FIV, they may nevertheless significantly reduce the impact of infection.
authors.affiliation: Retrovirus Research Laboratory, Department of Veterinary Pathology, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, UK. s.dunham@vet.gla.ac.uk
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Dunham
authors.forename: J Norman
authors.initials: JN
authors.lastname: Flynn
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rigby
authors.forename: Julie
authors.initials: J
authors.lastname: Macdonald
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bruce
authors.forename: Celia
authors.initials: C
authors.lastname: Cannon
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Golder
authors.forename: Linda
authors.initials: L
authors.lastname: Hanlon
authors.forename: David A
authors.initials: DA
authors.lastname: Harbour
authors.forename: Nancy A
authors.initials: NA
authors.lastname: Mackay
authors.forename: Norman
authors.initials: N
authors.lastname: Spibey
authors.forename: Oswald
authors.initials: O
authors.lastname: Jarrett
authors.forename: James C
authors.initials: JC
authors.lastname: Neil
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D001483:Base Sequence; D002415:Cats; D004279:DNA, Viral / Q000235:genetics; D003673:Defective Viruses / Q000201:enzymology / Q000235:genetics / Q000276:immunology; D016181:Feline Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D005814:Genes, Viral; D016089:Immunodeficiency Virus, Feline / Q000201:enzymology / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D019426:Integrases / Q000235:genetics; D018664:Interleukin-12 / Q000008:administration & dosage; D020382:Interleukin-18 / Q000008:administration & dosage; D008969:Molecular Sequence Data; D011533:Proviruses / Q000302:isolation & purification; D012194:RNA-Directed DNA Polymerase / Q000235:genetics; D017384:Sequence Deletion; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000494:pharmacology*; D014765:Viral Vaccines / Q000008:administration & dosage / Q000494:pharmacology*; D014774:Virulence; D014779:Virus Replication / Q000235:genetics
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D020382:Interleukin-18; D019444:Vaccines, DNA; D014765:Viral Vaccines; D018664:Interleukin-12; D019426:Integrases; D012194:RNA-Directed DNA Polymerase