Protective Immunity against Feline Immunodeficiency Virus Induced by Inoculation with vif-Deleted Proviral DNA

• Published in: Virology (New York, N.Y.) N.Y.), 2000-07, Vol.273 (1), p.67-79
• Main Authors: Lockridge, Kristen M., Chien, May, Dean, Gregg A., Stefano Cole, Kelly, Montelaro, Ronald C., Luciw, Paul A., Sparger, Ellen E.
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Animals; Antibodies, Viral - immunology; Antigens, Viral - immunology; Cats; DNA, Viral - administration & dosage; DNA, Viral - analysis; DNA, Viral - genetics; Env protein; Feline immunodeficiency virus; Gag protein; Gene Deletion; Gene Products, env - immunology; Gene Products, gag - immunology; Gene Products, vif - genetics; Genome, Viral; Immunodeficiency Virus, Feline - genetics; Immunodeficiency Virus, Feline - immunology; Immunodeficiency Virus, Feline - physiology; Lentivirus Infections - immunology; Lentivirus Infections - prevention & control; Lentivirus Infections - virology; Lymphocyte Count; Proviruses - genetics; T-Lymphocytes, Cytotoxic - immunology; Time Factors; Vaccines, DNA - genetics; Vaccines, DNA - immunology; vif gene; Viral Vaccines - genetics; Viral Vaccines - immunology
• ISSN: 0042-6822; 1096-0341
• DOI: 10.1006/viro.2000.0395

To determine whether live-attenuated feline immunodeficiency virus (FIV) proviral DNA will induce protective immunity, a plasmid clone constructed with a FIV provirus containing a deletion in the viral accessory gene vif (FIV-pPPR-Δvif) was inoculated as proviral DNA into four cats by the intramuscular route. After 43 weeks, these cats were boosted with the same proviral plasmid. Analysis of peripheral blood mononuclear cells at several time points after the primary and booster inoculations revealed no detectable virus or proviral DNA. At 6 weeks after the booster, immunized cats and additional naive control cats were challenged with a cell-free preparation of the infectious biological isolate FIV-PPR by the intraperitoneal route. Virus was detected after challenge in unvaccinated control cats but not in any of the FIV-pPPR-Δvif-immunized cats. Both FIV Gag- and Env-specific cytotoxic T lymphocyte (CTL) activities were detected in peripheral blood cells of control cats after challenge infection, whereas only one of four cats immunized with FIV-pPPR-Δvif DNA exhibited a measurable CTL response to Env following challenge. Although anti-Gag antibodies were not detected after both proviral DNA inoculation and challenge, anti-Env antibodies were found in FIV-pPPR-Δvif-immunized cats after vaccination as well as after challenge. These findings indicate that inoculation with FIV-pPPR-Δvif proviral DNA induced resistance to challenge with infectious FIV and that a vif deletion mutant may provide a relatively safe attenuated lentiviral vaccine.