Safety and immunogenicity of a high-titered canarypox vaccine in combination with rgp120 in a diverse population of HIV-1-uninfected adults: AIDS Vaccine Evaluation Group Protocol 022A.
To test the safety and immunogenicity of a high-titered preparation of ALVAC-HIV vCP205 in both high-risk and low-risk persons and to evaluate variations in dosing schedule, we conducted a multicenter, randomized, double-blind trial of this vector in combination with recombinant subunit gp120 in 150 HIV-1-seronegative volunteers. The high-titered ALVAC vaccine was well tolerated; adverse events were minimal and not influenced by dosing. At day 728, the cumulative probability of a cytotoxic T-lymphocyte (CTL) response was 76% (95% confidence interval [CI]: 64%-89%) among volunteers receiving vaccine, and the net amount attributable to vaccination was 50% (CI: 16%; 74%). The net probability of a repeated positive CTL response by day 728 was 50% (CI: 21%; 64%). There was a significant difference in CTL response at day 182 between volunteers who had received four doses versus three doses of vCP205 (42% vs. 24%, p =.052). The CTL response was similar in high-risk volunteers and vaccinia-naive volunteers compared with vaccinia-immune volunteers. Neutralizing antibody responses were detected in 95% of vaccinees at day 287, with higher geometric mean titers in recipients of sequential versus simultaneous dosing of the two vaccines and in vaccinia-naive volunteers. This high-titered preparation of ALVAC-HIV vCP205 in combination with gp120 was safe and immunogenic in a diverse group of HIV-1-seronegative volunteers.
Gupta
Kalpana
K
Department of Medicine, University of Washington, Seattle, Washington, USA.
Hudgens
Michael
M
Corey
Lawrence
L
McElrath
M Juliana
MJ
Weinhold
Kent
K
Montefiori
David C
DC
Gorse
Geoffrey J
GJ
Frey
Sharon E
SE
Keefer
Michael C
MC
Evans
Thomas G
TG
Dolin
Raphael
R
Schwartz
David H
DH
Harro
Clayton
C
Graham
Barney
B
Spearman
Paul W
PW
Mulligan
Mark
M
Goepfert
Paul
P
D016915:AIDS Vaccines / Q000009:adverse effects* / Q000235:genetics / Q000276:immunology*; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000009:adverse effects / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000175:diagnosis; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007115:Immunization Schedule; D008297:Male; D009500:Neutralization Tests; D011994:Recombinant Proteins / Q000009:adverse effects / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic
D016915:AIDS Vaccines; C106488:ALVAC-HIV-1 vCP250; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D011994:Recombinant Proteins; D017778:Vaccines, Combined; D014614:Vaccines, Synthetic