title: Simian immunodeficiency virus (SIV) gag DNA-vaccinated rhesus monkeys develop secondary cytotoxic T-lymphocyte responses and control viral replication after pathogenic SIV infection.
abstract: The potential contribution of a plasmid DNA construct to vaccine-elicited protective immunity was explored in the simian immunodeficiency virus (SIV)/macaque model of AIDS. Making use of soluble major histocompatibility class I/peptide tetramers and peptide-specific killing assays to monitor CD8(+) T-lymphocyte responses to a dominant SIV Gag epitope in genetically selected rhesus monkeys, a codon-optimized SIV gag DNA vaccine construct was shown to elicit a high-frequency SIV-specific cytotoxic T-lymphocyte (CTL) response. This CTL response was demonstrable in both peripheral blood and lymph node lymphocytes. Following an intravenous challenge with the highly pathogenic viral isolate SIVsm E660, these vaccinated monkeys developed a secondary CTL response that arose with more rapid kinetics and reached a higher frequency than did the postchallenge CTL response in control plasmid-vaccinated monkeys. While peak plasma SIV RNA levels were comparable in the experimentally and control-vaccinated monkeys during the period of primary infection, the gag plasmid DNA-vaccinated monkeys demonstrated better containment of viral replication by 50 days following SIV challenge. These findings indicate that a plasmid DNA vaccine can elicit SIV-specific CTL responses in rhesus monkeys, and this vaccine-elicited immunity can facilitate the generation of secondary CTL responses and control of viral replication following a pathogenic SIV challenge. These observations suggest that plasmid DNA may prove a useful component of a human immunodeficiency virus type 1 vaccine.
authors.affiliation: Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. eganm@WAR.Wyeth.com
authors.forename: M A
authors.initials: MA
authors.lastname: Egan
authors.forename: W A
authors.initials: WA
authors.lastname: Charini
authors.forename: M J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: J E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: P
authors.initials: P
authors.lastname: Racz
authors.forename: K
authors.initials: K
authors.lastname: Tenner-Racz
authors.forename: K
authors.initials: K
authors.lastname: Manson
authors.forename: M
authors.initials: M
authors.lastname: Wyand
authors.forename: M A
authors.initials: MA
authors.lastname: Lifton
authors.forename: C E
authors.initials: CE
authors.lastname: Nickerson
authors.forename: T
authors.initials: T
authors.lastname: Fu
authors.forename: J W
authors.initials: JW
authors.lastname: Shiver
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D015683:Gene Products, gag / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008198:Lymph Nodes / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D012367:RNA, Viral / Q000032:analysis; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology* / Q000517:prevention & control / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000502:physiology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014611:Vaccination; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*; D019562:Viral Load; D014779:Virus Replication
chemical_list: D015683:Gene Products, gag; D012367:RNA, Viral; D018449:SAIDS Vaccines; D019444:Vaccines, DNA