Background:  HIV recombinant canarypox (ALVAC-vCP1452) vaccine has been shown to be immunogenic. The goal of the ORVACS MANON-02 study was to evaluate, using 2 schedules, whether this immunogenicity could be improved with a homologous prime-boost strategy of immunization.

Methods:  Chronically HIV-infected, HAART-treated patients were randomized in an international, multicenter, double blind, placebo-controlled phase II clinical trial study to receive 4 (arm A: day 0 and  weeks 4, 8, and 20) or 3 (arm B:  weeks 4, 8, and 20) vaccine injections of vCP1452 or placebo (arm C). Patients were invited to interrupt HAART at week 24 and monitored until week 48. The primary end-point was the evaluation of the immunogenicity measured by ELISpot and defined as the change in frequencies of interferon-gamma (IFN-γ) -producing HIV-specific peripheral blood mononuclear cells (PBMC) between baseline and week 24 in the immunized arms compared to placebo. Vector-specific immunogenicity was measured by ELISpot. HIV-specific CD4 and CD8 function and differentiation were analyzed by intra-cellular cytokine staining. Secondary endpoints included evaluation of the immunization efficacy on HIV replication after discontinuation of HAART.

Results:  We present here the primary endpoint results of the study. Between April 2004 and July 2005, we enrolled 65 patients (median CD4:  653, 618, and 588 cells/mm³ in arms A, B, and C, respectively). No vaccine-related unsolicited adverse events were observed. At study baseline the median frequency of IFN-γ-producing HIV-specific PBMC did not differ among arms A, B, and C (mean: 1203, 1009, 1095 SFC/10⁶ PBMC). At week 24 the frequency of PBMC producing IFN-g significantly increased from baseline in the 4-injections arm but not in the 3-injections arm, compared to placebo (+480, +322, +8 SFC/10⁶ PBMC; p = 0.014 ). The frequency of IFN-g-producing PBMC against canarypox, barely detectable at baseline, increased significantly (p = 0.005) though weakly after 3 injections in both immunized arms. A total of 55 patients interrupted HAART at week 24 among whom 21 were still off treatment at week 48.

Conclusions:  This study is the first placebo-controlled study that demonstrates in chronically infected patients treated with HAART the significant T-cell immunogenicity of the HIV-recombinant canarypox vaccine (vCP1452) used alone. Compared to placebo, 4 vaccine injections proved to be more immunogenic than 3, despite a weak response against the vector. This study opens perspectives for continuing to explore clinical benefits of therapeutic vaccination.