title: Recombinant poxvirus boosting of DNA-primed rhesus monkeys augments peak but not memory T lymphocyte responses.
abstract: Although a consensus has emerged that an HIV vaccine should elicit a cytotoxic T lymphocyte (CTL) response, the characteristics of an effective vaccine-induced T lymphocyte response remain unclear. We explored this issue in the simian human immunodeficiency virus/rhesus monkey model in the course of assessing the relative immunogenicity of vaccine regimens that included a cytokine-augmented plasmid DNA prime and a boost with DNA or recombinant pox vectors. Recombinant vaccinia virus, recombinant modified vaccinia Ankara (MVA), and recombinant fowlpox were comparable in their immunogenicity. Moreover, whereas the magnitude of the peak vaccine-elicited T lymphocyte responses in the recombinant pox virus-boosted monkeys was substantially greater than that seen in the monkeys immunized with plasmid DNA alone, the magnitudes of recombinant pox boosted CTL responses decayed rapidly and were comparable to those of the DNA-alone-vaccinated monkeys by the time of viral challenge. Consistent with these comparable memory T cell responses, the clinical protection seen in all groups of experimentally vaccinated monkeys was similar. This study, therefore, indicates that the steady-state memory, rather than the peak effector vaccine-elicited T lymphocyte responses, may be the critical immune correlate of protection for a CTL-based HIV vaccine.
authors.affiliation: Division of Viral Pathogenesis, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
authors.forename: Dan H
authors.initials: DH
authors.lastname: Barouch
authors.forename: Birgit
authors.initials: B
authors.lastname: Korioth-Schmitz
authors.forename: Carol I
authors.initials: CI
authors.lastname: Lord
authors.forename: Georgia R
authors.initials: GR
authors.lastname: Krivulka
authors.forename: Faye
authors.initials: F
authors.lastname: Yu
authors.forename: Margaret H
authors.initials: MH
authors.lastname: Beddall
authors.forename: Darci A
authors.initials: DA
authors.lastname: Gorgone
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Lifton
authors.forename: Ayako
authors.initials: A
authors.lastname: Miura
authors.forename: Valerie
authors.initials: V
authors.lastname: Philippon
authors.forename: Kelledy
authors.initials: K
authors.lastname: Manson
authors.forename: Phillip D
authors.initials: PD
authors.lastname: Markham
authors.forename: John
authors.initials: J
authors.lastname: Parrish
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kuroda
authors.forename: Jörn E
authors.initials: JE
authors.lastname: Schmitz
authors.forename: Rebecca S
authors.initials: RS
authors.lastname: Gelman
authors.forename: John W
authors.initials: JW
authors.lastname: Shiver
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Dennis
authors.initials: D
authors.lastname: Panicali
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
mesh_terms: D000818:Animals; D018791:CD4 Lymphocyte Count; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D007156:Immunologic Memory; D018655:Lymphocyte Count; D008253:Macaca mulatta; D016133:Polymerase Chain Reaction / Q000379:methods; D011212:Poxviridae / Q000235:genetics*; D012367:RNA, Viral / Q000276:immunology; D015183:Restriction Mapping; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014616:Vaccinia virus / Q000235:genetics; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D012367:RNA, Viral; D014765:Viral Vaccines