title: High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects.
abstract: BACKGROUND
  In clinical trials, canarypox ALVAC-human immunodeficiency virus (HIV) vaccines have been shown to elicit human HIV-specific cytotoxic T lymphocyte (CTL) responses in some but not all healthy uninfected adults.Methods. A clinical trial was conducted to examine whether the vaccine vCP1452 would elicit a greater HIV-specific CTL response when given at a dose of 10(8.0) TCID50 (60 participants) than when given at the regular dose, 10(7.26) TCID50 (40 participants); as a control, a placebo vaccine preparation also was administered (10 participants).
  
  
  RESULTS
  Two weeks after the last vaccination in a series, HIV-specific CTL responses were not significantly different when measured by either chromium-release assay (8% and 16% in the high- and regular-dose recipients, respectively) or interferon- gamma ELISpot assay (8% and 15% in the high- and regular-dose recipients, respectively); moreover, recipients of the higher dose had greater local and systemic reactions (P<.001).
  
  
  CONCLUSIONS
  High reactogenicity associated with an increased dose of vCP1452 negates the need for further evaluation of this strategy to boost the frequency of HIV-specific CTL response in seronegative human subjects. Development of highly immunogenic canarypox vectors requires further work to optimize vector and insert design, as well as novel ways to increase dosage and to reduce reactogenicity.
authors.affiliation: Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-2050, USA. paulg@uab.edu
authors.forename: Paul A
authors.initials: PA
authors.lastname: Goepfert
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gurunathan
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Mary
authors.initials: M
authors.lastname: Allen
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Chiu
authors.forename: Paul
authors.initials: P
authors.lastname: Spearman
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Fuchs
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Koblin
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.forename: Sharon
authors.initials: S
authors.lastname: Frey
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000235:genetics / Q000276:immunology; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D018023:HIV Seronegativity / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D011994:Recombinant Proteins / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D016896:Treatment Outcome; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000008:administration & dosage* / Q000276:immunology; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D016915:AIDS Vaccines; C468116:ALVAC-HIV vCP1452; D015483:HIV Antibodies; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D007371:Interferon-gamma