OA05.03
Background: GV-TH-01, a Phase 1 open-label trial of GOVX-B11, a DNA/MVA prime-boost regimen, in HIV infected patients on ART was undertaken to evaluate safety and vaccine-elicited T cell responses, and to explore viral rebound during analytical treatment interruption (TI).
Methods: Patients who began ART within 18 months of seroconversion and had sustained plasma HIV-1 RNA<50 c/mL for at least 6 months were enrolled. Patients received a total of 4 inoculations at intervals of 8 weeks. 2 of pGA2/JS7 DNA (3mg) followed by 2 of MVA/HIV62B (108 TCID50). At 8 weeks after the last immunization, plus an efavirenz wash-out if needed, participants entered a TI phase of 12 weeks, after which ART was reinstituted. T cell responses were scored for IFNg or IL2 by flow cytometry following stimulation with Gag, Env and Pol peptides. Responses were considered positive if ≥2-fold higher than pre-vaccination.
Results: 8 of 9 men completed all vaccinations. For the 8, median age was 37.5 yrs, baseline CD4 count was 691/μL (501-1612/μl) and all had HIV-1 RNA<50 c/mL. Median viral load prior to ART was 5.1 log10 c/mL (2.6-7.2 log10 c/mL). No serious adverse events occurred. After the 1st or 2nd MVA/HIV62B immunization, Gag-specific CD8 T cells were boosted over pre-vaccination levels in 7 out of 8 (P<0.05) whereas Gag-specific CD4 T cells were boosted in 5 of 8 patients (P=0.2). 6 of 8 patients elicited previously undetectable CD8 responses whereas 5 of 8 elicited previously undetectable CD4 responses to Gag epitopes. Gp120 or gp41-specific antibody responses were boosted in 3 of 8 patient and 2 of 8 patients respectively. Excluding one acute seroconverter, the median reduction in HIV-1 RNA at weeks 2, 6, and 12 compared to pre-ART levels was −2.2, −1.3 and −0.8 log10 c/mL.
Conclusions: This trial demonstrates the potential for GOVX-B11 to boost both T cell and antibody responses in a therapeutic setting. A placebo-controlled trial will be required to further assess the therapeutic benefit of the vaccine.
