Microbiology & Immunology - Research Publications

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    Subtype AE HIV-1 DNA and recombinant Fowlpoxvirus vaccines encoding five shared HIV-1 genes: safety and T cell immunogenicity in macaques
    De Rose, R ; Chea, S ; Dale, CJ ; Reece, J ; Fernandez, CS ; Wilson, KM ; Thomson, S ; Ramshaw, IA ; Coupar, BEH ; Boyle, DB ; Sullivan, MT ; Kent, SJ (ELSEVIER SCI LTD, 2005-03-14)
    To induce broad T cell immunity to HIV-1, we evaluated the safety, immunogenicity and dose-response relationship of DNA and recombinant Fowlpoxvirus (rFPV) vaccines encoding five shared HIV subtype AE genes (Gag, Pol, Env, Tat, Rev) in pigtail macaques. The DNA (three doses of either 1 mg or 4.5 mg) and rFPV (a single boost of either 5 x 10(7) or 2 x 10(8) plaque forming units) vaccines were administered intramuscularly without adjuvants. Broadly reactive HIV-specific T cell immunity was stimulated by all doses of the vaccines administered, without significant differences between the high and low doses studied. The vaccines induced both CD4 and CD8 T cell responses to Gag, Pol, Env and Tat/Rev proteins, with CD4 T cell responses being greater in magnitude than CD8 T cell responses. The vaccine-induced T cell responses had significant cross-recognition of heterologous HIV-1 proteins from non-AE HIV-1 subtypes. In conclusion, these subtype AE HIV-1 DNA and rFPV vaccines were safe, induced broad T-cell immunity in macaques, and are suitable for progression into clinical trials.
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    Efficacy of DNA and fowlpox virus priming/boosting vaccines for simian/human immunodeficiency virus
    Dale, CJ ; De Rose, R ; Stratov, I ; Chea, S ; Montefiori, DC ; Thomson, S ; Ramshaw, IA ; Coupar, BEH ; Boyle, DB ; Law, M ; Kent, SJ (AMER SOC MICROBIOLOGY, 2004-12)
    Further advances are required in understanding protection from AIDS by T-cell immunity. We analyzed a set of multigenic simian/human immunodeficiency virus (SHIV) DNA and fowlpox virus priming and boosting vaccines for immunogenicity and protective efficacy in outbred pigtail macaques. The number of vaccinations required, the effect of DNA vaccination alone, and the effect of cytokine (gamma interferon) coexpression by the fowlpox virus boost was also studied. A coordinated induction of high levels of broadly reactive CD4 and CD8 T-cell immune responses was induced by sequential DNA and fowlpox virus vaccination. The immunogenicity of regimens utilizing fowlpox virus coexpressing gamma interferon, a single DNA priming vaccination, or DNA vaccines alone was inferior. Significant control of a virulent SHIV challenge was observed despite a loss of SHIV-specific proliferating T cells. The outcome of challenge with virulent SHIV(mn229) correlated with vaccine immunogenicity except that DNA vaccination alone primed for protection almost as effectively as the DNA/fowlpox virus regimen despite negligible immunogenicity by standard assays. These studies suggest that priming of immunity with DNA and fowlpox virus vaccines could delay AIDS in humans.
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    Analysis of Pigtail Macaque Major Histocompatibility Complex Class I Molecules Presenting Immunodominant Simian Immunodeficiency Virus Epitopes
    SMITH, MIRANDA ZOE DENHAM ; DALE, CAROLINE JANE HUGHES ; DE ROSE, ROBERT ; STRATOV, IVAN ; FERNANDEZ, CAROLINE SHAMALA ; BROOKS, ANDREW GEOFFREY ; WEINFURTER, JASON ; KREBS, KENDALL ; RIEK, CARA ; WATKINS, DAVID ; O'CONNOR, DAVID ; KENT, STEPHEN JOHN ( 2004)