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220 Immunization with Tat and Rev Induces Partial Protection from Mucosal SHIV Infection in Rhesus Macaques
B. Verrier*, R. Le Grand, C. Coiffier, Y. Ataman, B. Hurtrel, R. Gruters, A.-M. Aubertin, A. Osterhaus, G. Sutter, V. Erfle, B. Vaslin, and M. Girard
UMR CNRS-bioMérieux, CERVI, Lyon, France; CEA, Fontenay-aux-Roses, France; Inst. Pasteur, Paris, France; INSERM U 74, Strasbourg, France; GSF Inst. für Biologie, Munich, Germany; and Eramus Univ., Rotterdam, The Netherlands
Background: Recent evidence suggests that Tat-specific CTLs may be significantly involved in controlling simian immunodeficiency virus (SIV) infection.
Methods: To test whether vaccination with Tat or Tat and Rev could significantly reduce virus replication in nonhuman primates, rhesus macaques were primed with Semliki Forest Virus (SFV) expressing HIV-1 tat (SFV-tat) and HIV-1 rev (SFV-rev) and boosted with modified vaccinia virus Ankara expressing the same genes (MVA-tat and MVA-rev). Another group of monkeys was primed with SFV-tat only and boosted with MVA-tat. A third group of monkeys received a tat and rev DNA prime/MVA boost vaccine regimen. The animals were challenged by the rectal route at 9 weeks after the last booster immunization, using 10 MID50 of a stock of SHIV-BX08 grown in human PBMC. SHIV-BX08 contains the env, tat, and rev genes from primary isolate HIV-1 BX08. It was passaged 3 times in rhesus monkeys, but has kept the "R5," NSI phenotype of HIV-1 BX08. Post-challenge follow-up of the monkeys included testing seroconversion to Gag and Env antigens, measuring virus infectivity in PBMC by cocultivation with human indicator cells in limited dilution assays, and measuring copy number of viral RNA in plasma by RT-PCR.
Results: Viral loads remained below 1,500 copy/ml in 2 of 12 monkeys in the SFV prime/MVA boost groups and in 2 of 6 monkeys in the DNA prime/MVA boost group. These monkeys remained virus negative in their PBMC and showed no seroconversion to Gag or Env. Two other monkeys in the SFV/MVA group showed reduced virus loads (< 3,500 copy/ml) and lower number of infected cells but seroconverted to Gag and Rev. All other animals, including the 7 controls, showed high viral RNA loads, high cellular viremia, and became Western-blot positive.
Conclusions: These results suggest that Tat and Rev may be useful components in HIV vaccines.
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