Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer.
The utility of modified vaccinia virus Ankara (MVA) as a vector for eliciting AIDS virus-specific cytotoxic T lymphocytes (CTL) was explored in the simian immunodeficiency virus (SIV)/rhesus monkey model. After two intramuscular immunizations with recombinant MVA-SIVSM gag pol, the monkeys developed a Gag epitope-specific CTL response readily detected in peripheral blood lymphocytes by using a functional killing assay. Moreover, those immunizations also elicited a population of CD8+ T lymphocytes in the peripheral blood that bound a specific major histocompatibility complex class I/peptide tetramer. These Gag epitope-specific CD8+ T lymphocytes also were demonstrated by using both functional and tetramer-binding assays in lymph nodes of the immunized monkeys. These observations suggest that MVA may prove a useful vector for an HIV-1 vaccine. They also suggest that tetramer staining may be a useful technology for monitoring CTL generation in vaccine trials in nonhuman primates and in humans.
Harvard Medical School, Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
A
A
Seth
I
I
Ourmanov
M J
MJ
Kuroda
J E
JE
Schmitz
M W
MW
Carroll
L S
LS
Wyatt
B
B
Moss
M A
MA
Forman
V M
VM
Hirsch
N L
NL
Letvin
D016915:AIDS Vaccines / Q000302:isolation & purification; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D000939:Epitopes; D015685:Fusion Proteins, gag-pol / Q000235:genetics / Q000276:immunology*; D005822:Genetic Vectors; D015395:Histocompatibility Antigens Class I / Q000737:chemistry / Q000235:genetics; D006801:Humans; D007114:Immunization; D008253:Macaca mulatta; D011487:Protein Conformation; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics* / Q000276:immunology*
D016915:AIDS Vaccines; D017931:DNA Primers; D000939:Epitopes; D015685:Fusion Proteins, gag-pol; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins