High-dose recombinant Canarypox vaccine expressing HIV-1 protein, in seronegative human subjects.
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.
Goepfert
Paul A
PA
Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294-2050, USA. paulg@uab.edu
Horton
Helen
H
McElrath
M Juliana
MJ
Gurunathan
Sanjay
S
Ferrari
Guido
G
Tomaras
Georgia D
GD
Montefiori
David C
DC
Allen
Mary
M
Chiu
Ya-Lin
YL
Spearman
Paul
P
Fuchs
Jonathan D
JD
Koblin
Beryl A
BA
Blattner
William A
WA
Frey
Sharon
S
Keefer
Michael C
MC
Baden
Lindsey R
LR
Corey
Lawrence
L
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*
D016915:AIDS Vaccines; C468116:ALVAC-HIV vCP1452; D015483:HIV Antibodies; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D007371:Interferon-gamma