Immunization with a modified vaccinia virus expressing simian immunodeficiency virus (SIV) Gag-Pol primes for an anamnestic Gag-specific cytotoxic T-lymphocyte response and is associated with reduction of viremia after SIV challenge

The immunogenicity and protective efficacy of a modified vaccinia virus Ank ara (MVA) recombinant expressing the simian immunodeficiency virus (SIV) Ga g-Pol proteins (MVA-gag-pol) was explored in rhesus monkeys expressing the major histocompatibility complex (MHC) class I allele, MamuA*01. Macaques r eceived four sequential intramuscular immunizations with the MVA-gag-pol re combinant virus or nonrecombinant MVA as a control. Gag-specific cytotoxic T-lymphocyte (CTL) responses were detected in all MVA-gag-pol-immunized mac aques by both functional assays and flow cytometric analyses of CD8(+) T ce lls that hound a specific MHC complex class I-peptide tetramer, with levels peaking after the second immunization. Following challenge with uncloned S IVsmE660, all macaques became infected; however, viral load set points were loner in MVA-gag-pol-immunized macaques than in the MVA-immunized control macaques. MVA-gag-pol-immunized macaques exhibited a rapid and substantial anamnestic CTL response specific for the p11C, C-M Gag epitope. The level a t which CTL stabilized after resolution of primary viremia correlated inver sely with plasma viral load set point (P = 0.03). Most importantly, the mag nitude of reduction in viremia in the vaccinees was predicted by the magnit ude of the vaccine-elicited CTL response prior to SIV challenge.