A randomized therapeutic vaccine trial of canarypox-HIV-pulsed dendritic cells vs. canarypox-HIV alone in HIV-1-infected patients on antiretroviral therapy

Abstract

Targeting canarypox (CP)-HIV vaccine to dendritic cells (DCs) elicits anti-HIV-1 immune responses in vitro. We conducted a phase I/II clinical trial to evaluate whether adding DC to a CP-HIV vaccine improved virologic control during analytic treatment interruption (ATI) in HIV-1-infected subjects. Twenty-nine subjects on suppressive antiretroviral therapy were randomized to vaccination with autologous DCs infected with CP-HIV+keyhole limpet hemocyanin (KLH) (arm A, n=14) or CP-HIV+KLH alone (arm B, n=15). The mean viral load (VL) setpoint during ATI did not differ between subjects in arms A and B. A higher percentage of subjects in the DC group had a VL setpoint < 5,000 c/mL during ATI (4/13 or 31% in arm A compared with 0/13 in arm B, p=0.096), but virologic control was transient. Subjects in arm A had a greater increase in KLH lymphoproliferative response than subjects in arm B; however, summed ELISPOT responses to HIV-1 antigens did not differ by treatment arm. We conclude that a DC-CP-HIV vaccine is well-tolerated in HIV-1-infected patients, but does not lower VL setpoint during ATI compared with CP-HIV alone. New methods to enhance the immunogenicity and antiviral efficacy of DC-based vaccines for HIV-1 infection are needed.

Trial registration: ClinicalTrials.gov NCT00026624.

Figures

Fig. 1

HIV-1-infected subjects on antiretroviral therapy with suppressed viral load were randomized to receive either CP-HIV or DCs + CP-HIV. Subjects were vaccinated at weeks 3, 7 and 15. Following vaccination, subjects underwent analytic treatment interruption. At weeks 3 and 7, subjects also received keyhole limpet hemocyanin (KLH). KLH was a control to determine whether priming of new immune responses occurred. DC, dendritic cells; CP-HIV, canarypox-HIV; ATI, analytic treatment interruption; ART, antiretroviral therapy; VL, viral load.

Fig. 2

Subject disposition. VL, viral load; DC, dendritic cell; CP-HIV, canarypox-HIV; Wk, week; ART, antiretroviral therapy.

Fig. 3

Lymphoproliferative responses to keyhole limpet hemocyanin (KLH) during vaccinations. Median values are plotted and bars represent the 25th–75th percentiles. SI, stimulation index; ATI, analytic treatment interruption.

Fig. 4

Summed ELISPOT responses to HIV-1 antigens in subjects who received DC + CP-HIV (group A) vs. subjects who received CP-HIV alone (group B). A responder is defined as a subject who has a ≥3-fold increase in summed ELISPOT response, that is also ≥30 spot-forming cells/106 peripheral blood mononuclear cells, to HIV-1 antigens from baseline to the maximum pre-ATI time point (i.e. maximum ELISPOT level at week 3, 7 or between weeks 16–19). ATI: analytic treatment interruption.

Fig. 5

Viral load (VL) rebound during analytic treatment interruption. The horizontal dotted line represents a VL of 5000c/mL. The red lines (all in arm A) designate VL curves for subjects who had a setpoint VL