Background
Dendritic cells (DCs) are potent inducers of immune responses and DC-based therapeutic HIV-1 vaccination has led to boosted HIV-specific immune responses and partial viral control in some studies. We therefore evaluated the safety and immunogenicity of autologous monocyte-derived DC vaccines matured with either IL-1β, IL-6, TNFα, and prostaglandin E2 (pgDC) or IL-1β, TNFα, IFNα2b, IFNγ, and poly I:C (alpha-1; a1DC), and pulsed with 1 of 2 antigen sources (HIVconsvX conserved pol/gag peptides or autologous inactivated HIV-1) or no antigen (control).
Methods
Eligible participants (ppts) were adults with HIV RNA <50 copies/ml and CD4 ≥350/mm3 on stable ART for ≥24 months. Ppts were randomized to 1 of 6 arms: a1DC/autoHIV, a1DC/peptides, a1DC alone, pgDC/autoHIV, pgDC/peptides, pgDC alone (2:2:1:2:2:1); 6 doses (107 cells) were administered subcutaneously at 4-week (w) intervals. Immunogenicity was assessed by IFN-γ-ELISPOT assay measured at baseline and 2w after the last vaccine dose. Virologic measures included single copy assay (SCA), cell-associated HIV RNA and DNA (CAR/D) and intact proviral DNA assay (IPDA). Linear mixed models were carried out to compare pre-specific comparisons.
Results
56 ppts were enrolled and 40 vaccinated (median age 54.8y; 85% male; 30% Black). Majority of those not vaccinated was due to failed autologous viral isolation (n=12). All ppts had 3 or more doses DC vaccine (90% had 6 doses). No related grade 3 or higher adverse events were observed. Mild-moderate self-limited injection site reactions occurred in 20-88% ppts across arms. Significant within arm mean increases in HIV-1-specific CD8+ responses from pre- to post-vaccine were observed to pol and gag (Figure), including in the DC alone arms, whereas responses to other viral antigens and the conserved peptide pools were less frequent. Changes in HIV-1-specific CD8+ T cell responses from pre- to post-vaccine were not statistically different comparing a1DC versus pgDC, autoHIV vs peptides, or antigen vs no antigen. No significant differences were found within or between arms in virologic outcomes (SCA, IPDA, CAR/D).
Conclusions
Administration of autologous DC HIV-1 vaccines was safe and well tolerated. Significant increases in HIV-1-specific immune responses were observed in some participants, but no differences were observed between DC product types. Autologous DC vaccine production is logistically complex and resource-intensive and may not offer significant advantages over other therapeutic HIV-1 vaccines.
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