Experimental vaccine protection against homologous and heterologous strains of feline immunodeficiency virus.

More than 90% of cats immunized with inactivated whole infected-cell or cell-free feline immunodeficiency virus (FIV) vaccines were protected against intraperitoneal infection with 10 50% animal infectious doses of either homologous FIV Petaluma (28 of 30 cats) or heterologous FIV Dixon strain (27 of 28 cats). All 15 control cats were readily infected with either strain of FIV. Protection appears to correlate with antiviral envelope antibody levels by a mechanism yet to be determined.

Experimental vaccine protection against feline immunodeficiency virus.

Infection of domestic cats with the feline immunodeficiency virus (FIV) represents an important veterinary health problem and a useful animal model for the development of vaccines against acquired immunodeficiency syndrome (AIDS). Two experimental FIV vaccines have been developed; one consisting of fixed infected cells (Vaccine 1), the other of inactivated whole virus (Vaccine 2). After 4-6 immunizations over 2-5 months, both vaccines induced a strong FIV-specific immune response including neutralizing antibody and T-cell proliferation. Vaccine 1 protected 6 of 9 and Vaccine 2 protected 5 of 6 recipient cats against any detectable infection with a low dose (10 animal ID50) of FIV given intraperitoneally 2 weeks after the final boost. One additional cat in each vaccine group had a transient infection at 5-7 weeks postchallenge following which virus could no longer be detected. Thus, a total of 13 of 15 vaccinated cats were protected against persistent infection. By contrast, 13 of 13 controls were persistently infected by this challenge. The infected cell vaccine failed to protect against a higher dose (5 x 10(4) ID50) of FIV. These results indicate that vaccine prophylaxis against natural FIV infection should be achievable and enhance optimism of the prospect of developing an effective AIDS vaccine for humans.

Development of IL-2-independent feline lymphoid cell lines chronically infected with feline immunodeficiency virus: importance for diagnostic reagents and vaccines.

Two interleukin 2 (IL-2)-independent feline immunodeficiency virus (FIV) producer cell lines (FL-4 and FL-6) were produced by selecting cells from an IL-2-dependent culture of mixed peripheral blood lymphocytes infected with FIV. The new cell lines have been stable for over 1 year and spontaneously produce FIV with an average reverse transcriptase titer of 300,000 cpm/ml and an average sucrose gradient purified viral protein concentration of 1 mg/l. FIV produced from these cultures is highly infectious in vitro and in vivo. The FL-6 cell line was phenotyped as expressing the feline CD8 and Pan-T antigens, while the FL-4 cell line expressed the CD4, CD8, and Pan-T antigens. Both cell lines, however, express high levels of viral core and envelope proteins. Paraformaldehyde-inactivated whole virus and similarly inactivated whole-cell virus preparations induced a strong antibody response to core and envelope antigens in immunized cats. The establishment of FIV-producing feline IL-2-independent peripheral blood lymphocyte lines should be valuable for the development of FIV-diagnostic reagents and vaccines and also as a model for human acquired immunodeficiency syndrome vaccine development.

The mutagenic properties of hexachloroacetone in short-term bacterial mutagen assay systems.

Hexachloroacetone, CCl3--CO--CCl3, reverts the Ames strains TA98 and TA100 but not the non-plasmid strains TA1537, TA1535 and TA1538. In the absence of solvent, the number of revertant colonies is 5 times the spontaneous reversion rate for TA100 and 10 times the spontaneous reversion rate for TA98 with 26 mg hexachloroacetone per plate. This effect is seen in the absence of rat liver microsomes. In dimethylsulfoxide (DMSO) solution a more complicated pattern is seen. In DMSO solution cooled between 18 and 20 degrees C, The maximum nuber of revertants is similar to that found in the absence of DMSO, but only 1.75 mg hexachloroacetone per plate is needed. When DMSO solution of hexachloroacetone is warmed above 20 degrees C, a yellow color develops and the solution becomes more toxic to the test bacteria. The maximum number of revertants is then produced at about 0.5 mg hexachloroacetone per plate. Hexachloroacetone is found to be active, without microsomal activation, in the E. coli WP-2 and E. coli rec-BC test systems. Hexachloroacetone readily reacts with water in DMSO solutions to form the non-mutagenic hexachloroacetone hydrate.