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%.

FIGURE 1

nAbs against HIV-1_MN in peripheral blood measured by vital dye neutralization assay. Antibody levels are expressed as log titers by day within group. Each box plot displays the 25th percentile, the median, and the 75th percentile. The whiskers on each box plot show the fifth and 95th percentiles, and n equals the number of subjects tested in each group at each time point. Titers <10 were set equal to 5 for computations. Pairwise differences between treatment groups were tested using the 2-sided nonparametric Wilcoxon rank sum test. When compared with placebo, statistically significant differences (*P ≤ 0.01) were detected in all vaccine groups at days 98, 182, and 364 and in group C at day 42.