Background:  There is an urgent need for alternative therapies with the potential to durably suppress viral replication following therapy discontinuation. Dendritic cell (DC)-based vaccination strategies have been shown to augment antigen specific immunity in HIV infection and cancer. This randomized, prospective, phase I trial was designed to evaluate the combination of viral suppression with restoration of immune function using highly conserved, HIV-1 peptide-pulsed, autologous DC vaccination in HIV-infected individuals on ART.

Methods:  A total of 18 HIV-infected, ART-treated (CD4 >400, viral load <50), HLA-A*0201 subjects received autologous DC vaccination either intravenously or subcutaneously. We administered 2 low-dose (1 to 3 X 10⁶ DC, n = 6) or high-dose (5 to 10 X 10⁶ DC, n = 12) vaccines 3 weeks apart following a standard leukapheresis. Vaccines were prepared from peripheral blood mononuclear cell (PBMC)-derived plastic adherent monocytes cultured in rhIL-4 and rhGM-CSF for 6 days. DC were matured overnight in interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and PGE2 and pulsed for 2 hours with 3 highly conserved HLA-A*0201 supertype HIV peptides (Gag:386-394, Env:134-142, Pol:498-506) and 1 HLA-A*0201 Influenza A matrix peptide (Flu:58-66). A positive response was defined as spot-forming cells (SFC) >2 SD and at least 20 spots per 10⁶ plated cells over background in interferon (IFN)-γ ELISpot assays. A vaccine-induced response was defined as a ≥3-fold increase in SFC over baseline and at least 100 SFC/10⁶ cells in response to at least 1 peptide at any time-point.

Results:  All subjects have completed scheduled vaccinations; the DC vaccines were generally well tolerated. One subject had a grade-4 fever after the first vaccination and did not receive the second. At baseline, 9 of 17 subjects responded to at least 1 HIV vaccine peptide and 11 of 17 responded to the Flu peptide. Of 17 subjects, 11 developed vaccine-induced responses with 5 responding to 2 or more peptides. Post-vaccination responses to each of the HIV peptides were observed:  Gag (7 subjects), Env (3), and Pol (5). No significant differences were noted between high and low dose or the intravenous and subcutaneous cohorts.    

Conclusions:  DC vaccination was safe and feasible in HIV-infected subjects on ART with virologic suppression. DC vaccination with selected HLA-A2 peptides was immunogenic in this cohort. Future, larger DC vaccine studies utilizing more broadly reactive antigens and clinical end-points are warranted.