title: 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.
abstract: 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.
authors.affiliation: Department of Medicine, University of Washington, Seattle, Washington, USA.
authors.forename: Kalpana
authors.initials: K
authors.lastname: Gupta
authors.forename: Michael
authors.initials: M
authors.lastname: Hudgens
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Kent
authors.initials: K
authors.lastname: Weinhold
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Gorse
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Evans
authors.forename: Raphael
authors.initials: R
authors.lastname: Dolin
authors.forename: David H
authors.initials: DH
authors.lastname: Schwartz
authors.forename: Clayton
authors.initials: C
authors.lastname: Harro
authors.forename: Barney
authors.initials: B
authors.lastname: Graham
authors.forename: Paul W
authors.initials: PW
authors.lastname: Spearman
authors.forename: Mark
authors.initials: M
authors.lastname: Mulligan
authors.forename: Paul
authors.initials: P
authors.lastname: Goepfert
mesh_terms: 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
chemical_list: 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