title: 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.
abstract: The immunogenicity and protective efficacy of a modified vaccinia virus Ankara (MVA) recombinant expressing the simian immunodeficiency virus (SIV) Gag-Pol proteins (MVA-gag-pol) was explored in rhesus monkeys expressing the major histocompatibility complex (MHC) class I allele, MamuA*01. Macaques received four sequential intramuscular immunizations with the MVA-gag-pol recombinant virus or nonrecombinant MVA as a control. Gag-specific cytotoxic T-lymphocyte (CTL) responses were detected in all MVA-gag-pol-immunized macaques by both functional assays and flow cytometric analyses of CD8(+) T cells that bound a specific MHC complex class I-peptide tetramer, with levels peaking after the second immunization. Following challenge with uncloned SIVsmE660, all macaques became infected; however, viral load set points were lower 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 at which CTL stabilized after resolution of primary viremia correlated inversely with plasma viral load set point (P = 0.03). Most importantly, the magnitude of reduction in viremia in the vaccinees was predicted by the magnitude of the vaccine-elicited CTL response prior to SIV challenge.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
authors.forename: A
authors.initials: A
authors.lastname: Seth
authors.forename: I
authors.initials: I
authors.lastname: Ourmanov
authors.forename: J E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: M J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: M A
authors.initials: MA
authors.lastname: Lifton
authors.forename: C E
authors.initials: CE
authors.lastname: Nickerson
authors.forename: L
authors.initials: L
authors.lastname: Wyatt
authors.forename: M
authors.initials: M
authors.lastname: Carroll
authors.forename: B
authors.initials: B
authors.lastname: Moss
authors.forename: D
authors.initials: D
authors.lastname: Venzon
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
authors.forename: V M
authors.initials: VM
authors.lastname: Hirsch
mesh_terms: D000818:Animals; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D008253:Macaca mulatta; D011237:Predictive Value of Tests; D018449:SAIDS Vaccines / Q000235:genetics / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000517:prevention & control*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus; D019562:Viral Load; D014766:Viremia / Q000276:immunology
chemical_list: D015685:Fusion Proteins, gag-pol; D018449:SAIDS Vaccines