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

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-08, Vol.95 (17), p.10112-10116
• Main Authors: Seth, Aruna, Ourmanov, Ilnour, Kuroda, Marcelo J., Schmitz, Jorn E., Carroll, Miles W., Wyatt, Linda S., Moss, Bernard, Forman, Meryl A., Hirsch, Vanessa M., Letvin, Norman L.
• Format: Article
• Language: English
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS Vaccines - isolation & purification; Animals; Base Sequence; Biological Sciences; Blood; Cell lines; DNA Primers - genetics; Epitopes; Fusion Proteins, gag-pol - genetics; Fusion Proteins, gag-pol - immunology; Genetic Vectors; Histocompatibility Antigens Class I - chemistry; Histocompatibility Antigens Class I - genetics; HIV 1; Humans; Immunization; Lymph nodes; Lymphocytes; Macaca mulatta; Medical research; Monkeys & apes; Peptides; Protein Conformation; Recombinant Proteins - genetics; Recombinant Proteins - immunology; Simian immunodeficiency virus; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - immunology; T lymphocytes; T-Lymphocytes, Cytotoxic - immunology; Vaccination; Vaccines; Vaccinia virus; Vaccinia virus - genetics; Vaccinia virus - immunology; Viruses
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.17.10112

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 intra-muscular immunizations with recombinant MVA-SIVSMgag 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.