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 inoculat ion of replication defective feline immunodeficiency virus proviral DNA (FI V Delta RT). 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, refra ctory to repeated DNA inoculations. Nevertheless, a significant proportion of the cats were protected from challenge with homologous virus. The effect s of interval between inoculations, route of DNA delivery, and promoter use d to regulate viral gene expression on the induction of virus-specific CTLs were evaluated. The highest levels of virus-specific lysis were recorded f ollowing intramuscular co-inoculation of FIV Delta RT and gamma-IFN DNA, wh ere FIV gene expression was under the control of a cytomegalovirus (CMV) pr omoter. However, the highest levels of protection were observed using the v iral 5'LTR as the promoter. These results suggest that a single intramuscul ar inoculation of FIV Delta RT DNA together with gamma-IFN DNA may be suffi cient to induce virus-specific CTLs and protection. (C) 2000 Elsevier Scien ce Ltd. All rights reserved.