Protection against feline immunodeficiency virus using replication defective proviral DNA vaccines with feline interleukin-12 and -18.
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.
Dunham
Stephen P
SP
Retrovirus Research Laboratory, Department of Veterinary Pathology, University of Glasgow Veterinary School, Bearsden Road, Glasgow G61 1QH, UK. s.dunham@vet.gla.ac.uk
Flynn
J Norman
JN
Rigby
Mark A
MA
Macdonald
Julie
J
Bruce
Jennifer
J
Cannon
Celia
C
Golder
Matthew C
MC
Hanlon
Linda
L
Harbour
David A
DA
Mackay
Nancy A
NA
Spibey
Norman
N
Jarrett
Oswald
O
Neil
James C
JC
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
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