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.
Seth
A
A
Harvard Medical School, Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Ourmanov
I
I
Kuroda
M J
MJ
Schmitz
J E
JE
Carroll
M W
MW
Wyatt
L S
LS
Moss
B
B
Forman
M A
MA
Hirsch
V M
VM
Letvin
N L
NL
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