Factors influencing cellular immune responses to feline immunodeficiency virus induced by DNA vaccination.
Virus-specific effector cytotoxic T lymphocytes (CTL) were elicited in the peripheral blood of domestic cats following a single intramuscular inoculation of replication defective feline immunodeficiency virus proviral DNA (FIVDeltaRT). Higher levels of virus-specific cytolysis were observed in the blood when cats were co-inoculated with feline gamma-interferon (IFN) DNA. The responses declined by 12 weeks following the first DNA inoculation and were, with the exception of FIV Gag-specific responses in some cats, refractory to repeated DNA inoculations. Nevertheless, a significant proportion of the cats were protected from challenge with homologous virus. The effects of interval between inoculations, route of DNA delivery, and promoter used to regulate viral gene expression on the induction of virus-specific CTLs were evaluated. The highest levels of virus-specific lysis were recorded following intramuscular co-inoculation of FIVDeltaRT and gamma-IFN DNA, where FIV gene expression was under the control of a cytomegalovirus (CMV) promoter. However, the highest levels of protection were observed using the viral 5'LTR as the promoter. These results suggest that a single intramuscular inoculation of FIVDeltaRT DNA together with gamma-IFN DNA may be sufficient to induce virus-specific CTLs and protection.
Flynn
J N
JN
Retrovirus Research Laboratory, Department of Veterinary Pathology, University of Glasgow, Bearsden, Glasgow, UK. n.flynn@vet.gla.ac.uk
Hosie
M J
MJ
Rigby
M A
MA
Mackay
N
N
Cannon
C A
CA
Dunsford
T
T
Neil
J C
JC
Jarrett
O
O
D000818:Animals; D002415:Cats; D003587:Cytomegalovirus / Q000235:genetics; D015686:Gene Products, env / Q000276:immunology; D015683:Gene Products, gag / Q000276:immunology; D016089:Immunodeficiency Virus, Feline / Q000276:immunology*; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000235:genetics*; D011401:Promoter Regions, Genetic; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D020079:Terminal Repeat Sequences; D019444:Vaccines, DNA / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology*
D015686:Gene Products, env; D015683:Gene Products, gag; D019444:Vaccines, DNA; D014765:Viral Vaccines; D007371:Interferon-gamma