title: Phase 2 study of an HIV-1 canarypox vaccine (vCP1452) alone and in combination with rgp120: negative results fail to trigger a phase 3 correlates trial.
abstract: BACKGROUND
  A goal of T-cell HIV vaccines is to define the correlation between a vaccine-induced immune response and protection from HIV infection. We conducted a phase 2 trial to determine if a canarypox vaccine candidate (vCP1452) administered with rgp120 subunit protein would "qualify" for a trial to define a correlate of efficacy.
  
  
  METHODS
  A total of 330 healthy volunteers were enrolled into 4 groups: 120 received vCP1452 alone (0, 1, 3, and 6 months), 120 received vCP1452 with 2 different regimens of rgp120 coadministration, and 90 received placebo. HIV-specific antibody responses were measured by enzyme-linked immunoassay (ELISA) and neutralizing activity. T-cell responses were measured by chromium release and interferon-gamma (IFNgamma) enzyme-linked immunospot (ELISpot) assay.
  
  
  RESULTS
  Significant neutralizing antibody responses to the HIV MN strain were detected in all vaccine groups, with net responses ranging from 57% (95% confidence interval [CI]: 40% to 71%) to 94% (95% CI: 85% to 99%). Net cumulative HIV-specific CD8 IFNgamma ELISpot assay responses were 13% (95% CI: -1% to 26%) for recipients of vCP1452 alone and 16% (95% CI: 2% to 29%) for recipients of vCP1452 plus rgp120.
  
  
  CONCLUSIONS
  Overall, the HIV-specific CD8 cytotoxic T lymphocyte (CTL) response was not sufficient to qualify the regimen for a subsequent trial designed to detect an immune correlate of protection requiring a minimum CD8 CTL frequency of 30%.
authors.affiliation: Program in Infectious Diseases, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. nina.russell@gatesfoundation.org
authors.forename: Nina D
authors.initials: ND
authors.lastname: Russell
authors.forename: Barney S
authors.initials: BS
authors.lastname: Graham
authors.forename: Michael C
authors.initials: MC
authors.lastname: Keefer
authors.forename: M Juliana
authors.initials: MJ
authors.lastname: McElrath
authors.forename: Steve G
authors.initials: SG
authors.lastname: Self
authors.forename: Kent J
authors.initials: KJ
authors.lastname: Weinhold
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.forename: Guido
authors.initials: G
authors.lastname: Ferrari
authors.forename: Helen
authors.initials: H
authors.lastname: Horton
authors.forename: Georgia D
authors.initials: GD
authors.lastname: Tomaras
authors.forename: Sanjay
authors.initials: S
authors.lastname: Gurunathan
authors.forename: Lynn
authors.initials: L
authors.lastname: Baglyos
authors.forename: Sharon E
authors.initials: SE
authors.lastname: Frey
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Mulligan
authors.forename: Clayton D
authors.initials: CD
authors.lastname: Harro
authors.forename: Susan P
authors.initials: SP
authors.lastname: Buchbinder
authors.forename: Lindsey R
authors.initials: LR
authors.lastname: Baden
authors.forename: William A
authors.initials: WA
authors.lastname: Blattner
authors.forename: Beryl A
authors.initials: BA
authors.lastname: Koblin
authors.forename: Lawrence
authors.initials: L
authors.lastname: Corey
mesh_terms: D016915:AIDS Vaccines / Q000009:adverse effects / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D028121:Canarypox virus / Q000235:genetics; D002857:Chromium / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005822:Genetic Vectors; D015483:HIV Antibodies / Q000097:blood*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D008875:Middle Aged; D009500:Neutralization Tests; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000276:immunology
chemical_list: D016915:AIDS Vaccines; C112734:AIDSVAX; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D022223:Vaccines, Subunit; D014614:Vaccines, Synthetic; D002857:Chromium; D007371:Interferon-gamma