Vaccination with Autologous Dendritic Cells Pulsed with Autologous HIV-Infected Apoptotic Cells

Background: We evaluated the safety, tolerability, and immunogenicity of a therapeutic HIV vaccine composed of autologous dendritic cells (DC) pulsed with autologous, inactivated, HIV-1 infected apoptotic cells (DC-HIV vaccine). Methodology: Autologous HIV-1 was isolated from ART-naive subjects who then initiated PI-based ART. DC-HIV vaccine was composed of autologous monocyte-derived DC (matured with TNFα, IL-1β, IFNγ, Poly I:C) pulsed with autologous lymphocytes infected with autologous HIV-1 and inactivated by UV/psoralen. After virologic suppression (<50 cps/mL) for at least 12 weeks, subjects received 3 doses (107 DC each) of DC-HIV vaccine subcutaneously, given at 2 week intervals, followed 6 weeks later by analytic treatment interruption (ATI). A 4th HIV-DC vaccine dose was given 2 weeks into ATI. The primary endpoint was change in HIV-1 RNA from pre-ART to 12 weeks after ATI. Polyfunctional CD8+ T cell responses to the vaccine (n=7) and to consensus HIV-1 Gag peptide pools (n=10) were evaluated before and after vaccination. Changes in T cell immune activation (DR+CD38+) and regulatory T cell (Treg) and myeloid-derived suppressor cell (MDSC) frequencies were also assessed. Results: Ten male subjects were enrolled and received study vaccine (pre-ART median CD4= 486 cells/mm3 and HIV-1 RNA=4.53 log10 copies/mL; median duration of HIV diagnosis= 27 mos). The DC-HIV vaccine was well-tolerated and caused only minor local reactions. All subjects remained off ART for the 12-week ATI. Three of 10 subjects had a ≥0.4 log10 decrease in HIV-1 RNA from their pre-ART baseline. CD8+ T cell polyfunctional response was increased in 3/7 subjects after ATI compared to the pre-vaccine response while on ART. Additionally, 4/10 subjects had an increase in CD8+ T cell polyfunctional response to Gag peptide but only 1/3 subjects with ≥0.4 log decrease in HIV-1 RNA had an increase in response to Gag peptide. There was an increase in CD4+ (p=0.006; Wilcoxon signed rank test) and CD8+ (p=0.007) T cell activation following the first vaccine dose but this returned to pre-vaccine baseline 6 weeks after the 3rd vaccine dose. No change in Treg frequency after vaccination was observed but MDSC frequency was increased (median=2.67-fold; P<0.006). MDSC frequencies remained increased through the 12-week ATI. Conclusions: DC-HIV vaccination was safe and well tolerated, and associated with a decrease in plasma HIV-1 RNA in some subjects and an early and transient increase in both CD4+ and CD8+ T cell immune activation. Modest increases in CD8+ T cell anti-HIV-1 responses and a subsequent decrease of T cell activation to baseline levels may be related to enhanced frequencies of MDSCs induced by the DC vaccine.