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

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 groups120 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-γ (IFNγ) 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% CI85% to 99%). Net cumulative HIV-specific CD8 IFNγ ELISpot assay responses were 13% (95% CI−1% to 26%) for recipients of vCP1452 alone and 16% (95% CI2% 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%.