AIDS Vaccination Studies Using an Ex Vivo Feline Immunodeficiency Virus Model: Protection from an Intraclade Challenge Administered Systemically or Mucosally by an Attenuated Vaccine

Abstract

Feline immunodeficiency virus (FIV) infection of domestic cats represents a valuable system through which to investigate criteria for antilentiviral vaccines in a natural host species. Here, we examined whether vaccination with a strain of FIV attenuated as a result of prolonged growth in vitro could protect against a fully virulent, highly heterologous intraclade challenge. The results indicated that the vaccine virus produced a low-grade infection with no detectable pathological effects and afforded a long-lasting sterilizing immunity if the challenge was delivered intraperitoneally as cell-free virus but not against a cell-associated intravaginal challenge. In the latter case, however, the replication and pathological consequences of the challenge virus were markedly suppressed. Together with similar results obtained in rhesus monkey models, these findings should give impulse to the development of attenuated FIV vaccines to be tested in controlled studies in field cats. Field studies may provide answers to some of the existing safety concerns surrounding attenuated AIDS vaccines in humans.

Puma Lentivirus Is Controlled in Domestic Cats after Mucosal Exposure in the Absence of Conventional Indicators of Immunity

“…Viremia after HIV, SIV, and FIV infection peaks early after infection and then declines to a steady-state level, presumably due to the initiation of a host immune response (19). Proviral load has been shown to follow a similar pattern in SIV and SHIV infections of monkeys (43) and in FIV infection in cats (42). PLV proviral loads were sustained throughout the 9-month study in four of four i.v.-inoculated and one of four mucosally exposed animals, but a gradual decline was noted over time, suggesting that these animals may have eventually eliminated PBMC provirus had they been monitored over a longer period of time.…”

“…Clinical monitoring was not measured intensively after this time, as all cats were consistently clinically normal. Blood samples were obtained by venipuncture of the jugular or cephalic vein on study days (relative to virus exposure) Ϫ1, 3,7,10,15,22,29,35,42,49,64,79,91,107,114,135,171,184,198,233,240,247,254, and 259.…”

Env-Expressing Autologous T Lymphocytes Induce Neutralizing Antibody and Afford Marked Protection against Feline Immunodeficiency Virus

“…Prior to any procedure, the animals were sedated with ketamine-diazepam intramuscularly. The challenge virus was FIV-Pet that had been consecutively passed in vivo several times and, as a result, had reacquired virulence and neutralization characteristics typical of those of wild-type FIV (53). The preparation used was pooled plasma from acutely infected SPF cats titrated in vivo, frozen in aliquots, and diluted when used to contain 10 50% cat infectious doses (CID 50 ) in 1 ml.…”

“…FIV Env was derived from pKKS ( Fig. 1A), a replication-competent molecular clone obtained by the cloning of env of in vivo-readapted FIV-Pet (4,53) into the p34TF10 backbone (GenBank accession no. NC_001482).…”

Feline Immunodeficiency Virus (FIV) Infection in Cats: A Possible Cause of Renal Pathological Changes

“…Seven-teen animals were inoculated with Petaluma (group 1), 28 with Pisa-M2 isolate (group 2), and 11 were first inoculated with Petaluma and, one year later, superinfected with Pisa-M2 (group 3). Petaluma isolate was obtained from supernatant of persistently infected FL4 cells [19], while Pisa-M2 was a local isolate propagated in vivo by monthly passages in SPF cats and never passaged in vitro [20]. Animals were inoculated intravenously with either 2 ml of freshly collected blood (Pisa-M2) or 20 cat infectious dose 50% of FL-4 supernatant (Petaluma).…”